PABPN1

-First Subject Dosed with BB-301 in Phase 1b/2a Clinical Treatment Study (NCT06185673) in November 2023- -Data Safety Monitoring Board Review for First Subject Completed After Day 28 Study Visit- -Second Subject Scheduled to Receive BB-301 in February 2024- -23 Subjects Enrolled into the Oculopharyngeal Muscular Dystrophy Natural History Study with Multiple Subjects Eligible for entry into the Phase 1b/2a Clinical Treatment Study in 2024- HAYWARD, Calif., Feb. 13, 2024 (GLOBE NEWSWIRE) -- Benitec Biopharma Inc. (NASDAQ: BNTC) (“Benitec” or “Company”), a clinical-stage, gene therapy-focused, biotechnology company developing novel genetic medicines based on its proprietary “Silence and Replace” DNA-directed RNA interference (“ddRNAi”) platform, today announced financial results for its second fiscal quarter ended December 31, 2023. The Company has filed its quarterly report on Form 10-Q with the U.S. Securities and Exchange Commission. “In 2023 we formally began the journey towards clinical validation of our Silence and Replace-based approach to the management of genetically defined disorders, and our central goals remain focused on the improvement of the lives of patients suffering from Oculopharyngeal Muscular Dystrophy,” said Jerel A. Banks, M.D., Ph.D., Executive Chairman and Chief Executive Officer of Benitec. “No dose-limiting toxicities have been observed in the first subject treated with BB-301, and the Data Safety Monitoring Board recommended the continuation of subject enrollment for the Phase 1b/2a Clinical Treatment Study without any modifications to the study. We are grateful to have the opportunity to continue the clinical evaluation of BB-301, and we look forward to reporting interim safety data and efficacy data in mid-2024.” Operational Updates The key milestones related to the development of BB-301 for the treatment of Oculopharyngeal Muscular Dystrophy (OPMD)-related Dysphagia, along with other corporate updates, are outlined below: BB-301 Clinical Development Program Overview: The BB-301 Phase 1b/2a clinical development program is currently underway in the United States, and the primary elements of the program are summarized below: The program comprises 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-related 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). BB-301 will be delivered directly into the pharyngeal constrictor 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 Clinical Treatment Study (NCT06185673), with interim safety and efficacy results expected to be available at the end of each 90-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”). 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)2Pharyngeal 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)2Normalized Residue Ratio Scale (NRRSv, NRRSp)Pharyngeal Construction Ratio (PCR) The OPMD 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 OPMD NH Study, participants will, potentially, be eligible for enrollment into the BB-301 Phase 1b/2a Clinical Treatment Study (NCT06185673).BB-301 Phase 1b/2a Clinical Treatment Study (NCT06185673): This first-in-human (FIH) study is evaluating the safety and clinical activity of intramuscular doses of BB-301 administered to subjects with OPMD-related Dysphagia.The primary endpoint of the FIH Study is 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. Critically, each of the clinical and videofluoroscopic assessments employed in the FIH Study will be equivalent to those employed for the OPMD 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 natural history of dysphagia observed for each OPMD NH Study participant, as characterized by the VFSS, clinical assessments of global swallowing capacity, and patient-reported outcome measures conducted during the OPMD NH Study, will serve as the baseline for comparative assessments of safety and efficacy of BB-301 upon rollover from the OPMD NH Study onto the BB-301 Phase 1b/2a Clinical Treatment Study (NCT06185673). Corporate Updates: As of January 2024, 23 subjects have been enrolled into the OPMD NH Study in the United States, and the BB-301 development program is designed to treat 21-to-30 subjects.In accordance with the Protocol for the BB-301 Phase 1b/2a Clinical Treatment Study (NCT06185673), a meeting of the Data Safety Monitoring Board (DSMB) was convened in January 2024 following the completion of the 28-day post BB-301 dosing visit. No dose-limiting toxicities were observed in the first subject treated with BB-301, and the DSMB recommended the continuation of subject enrollment for the Phase 1b/2a Clinical Treatment Study without any modifications to the study. Following the DSMB recommendation, a second subject has been scheduled to receive BB-301 in February 2024. The next DSMB meeting is anticipated to occur in June 2024 following the 28-day post BB-301 dosing visit of the third subject in Cohort 1 of the BB-301 Phase 1b/2a Clinical Treatment Study (NCT06185673).Interim safety data and efficacy data are expected to become available from the BB-301 Phase 1b/2a Clinical Treatment Study (NCT06185673) in mid-2024. Financial Highlights Second Quarter 2024 Financial Results Total Revenues for the quarter ended December 31, 2023, were $0 compared to $14,000 in licensing revenues collected for the quarter ended December 31, 2022. Total Expenses for the quarter ended December 31, 2023, were $6.9 million compared to $5.6 million for the quarter ended December 31, 2022. For the quarter ended December 31, 2023, the Company incurred royalties and license fees of $1,000 compared to $0 for the three months ended December 31, 2022. The Company incurred $5.1 million of research and development expenses compared to $3.8 million for the comparable quarter ended December 31, 2022. Research and development expenses relate primarily to ongoing clinical development of BB-301 for the treatment of OPMD. General and administrative expenses were $1.8 million compared to $1.9 million for the quarter ended December 31, 2022. The loss from operations for the quarter ended December 31, 2023, was $6.9 million compared to a loss of $5.6 million for the quarter ended December 31, 2022. Net loss attributable to shareholders for the quarter ended December 31, 2023, was $6.8 million, or $2.64 per basic and diluted share, compared to a net loss of $5.4 million, or $3.34 per basic and diluted share for the quarter ended December 31, 2022. As of December 31, 2023, the Company had $20.4 million in cash and cash equivalents. BENITEC BIOPHARMA INC.Consolidated Balance Sheets(in thousands, except par value and share amounts) December 31, June 30, 2023 2023 (Unaudited) Assets Current assets: Cash and cash equivalents$20,374 $2,477 Restricted cash 14 13 Trade and other receivables 53 55 Prepaid and other assets 355 1,184 Total current assets 20,796 3,729 Property and equipment, net 51 87 Deposits 25 25 Prepaid and other assets 81 97 Right-of-use assets 400 526 Total assets$21,353 $4,464 Liabilities and stockholders’ equity Current liabilities: Trade and other payables$4,937 $3,231 Accrued employee benefits 523 472 Lease liabilities, current portion 286 275 Total current liabilities 5,746 3,978 Lease liabilities, less current portion 137 284 Total liabilities 5,883 4,262 Commitments and contingencies (Note 11) Stockholders’ equity: Common stock, $0.0001 par value - 160,000,000 shares authorized; 2,592,434 shares and 1,671,485 shares issued and outstanding at December 31, 2023 and June 30, 2023, respectively — — Additional paid-in capital 197,063 168,921 Accumulated deficit (180,641) (167,889)Accumulated other comprehensive loss (952) (830)Total stockholders’ equity 15,470 202 Total liabilities and stockholders’ equity$21,353 $4,464 The accompanying notes are an integral part of these consolidated financial statements. BENITEC BIOPHARMA INC.Consolidated Statements of Operations and Comprehensive Loss(Unaudited)(in thousands, except share and per share amounts) Three Months Ended Six Months Ended December 31, December 31, 2023 2022 2023 2022Revenue: Licensing revenues from customers$— $14 $— $14 Total revenues — 14 — 14 Operating expenses: Royalties and license fees 1 — (105) — Research and development 5,102 3,761 9,531 6,421 General and administrative 1,824 1,863 3,375 3,783 Total operating expenses 6,927 5,624 12,801 10,204 Loss from operations (6,927) (5,610) (12,801) (10,190)Other income (loss): Foreign currency transaction gain (loss) 152 161 96 (346)Interest expense, net (6) (9) (12) (18)Other income (expense), net (16) 50 (34) 50 Unrealized loss on investment (1) (3) (1) — Total other income (loss), net 129 199 49 (314)Net loss$(6,798) $(5,411) $(12,752) $(10,504)Other comprehensive income (loss): Unrealized foreign currency translation gain (loss) (172) (160) (122) 347 Total other comprehensive income (loss) (172) (160) (122) 347 Total comprehensive loss$(6,970) $(5,571) $(12,874) $(10,157)Net loss$(6,798) $(5,411) $(12,752) $(10,504)Net loss per share: Basic and diluted$(2.64) $(3.34) $(5.39) $(9.30)Weighted average number of shares outstanding: basic and diluted 2,576,347 1,621,280 2,366,706 1,129,926 The accompanying notes are an integral part of these consolidated financial statements. About BB-301 BB-301 is a novel, modified AAV9 capsid expressing a unique, single bifunctional construct promoting co-expression of both codon-optimized Poly-A Binding Protein Nuclear-1 (PABPN1) and two small inhibitory RNAs (siRNAs) against mutant PABPN1. The two siRNAs are modeled into microRNA backbones to silence expression of faulty mutant PABPN1, while allowing expression of the codon-optimized PABPN1 to replace the mutant with a functional version of the protein. We believe the silence and replace mechanism of BB-301 is uniquely positioned for the treatment of OPMD by halting mutant expression while providing a functional replacement protein. About Benitec Biopharma, Inc. Benitec Biopharma Inc. (“Benitec” or the “Company”) is a clinical-stage biotechnology company focused on the advancement of novel genetic medicines with headquarters in Hayward, California. The proprietary “Silence and Replace” DNA-directed RNA interference platform combines RNA interference, or RNAi, with gene therapy to create medicines that simultaneously facilitate sustained silencing of disease-causing genes and concomitant delivery of wildtype replacement genes following a single administration of the therapeutic construct. The Company is developing Silence and Replace- based therapeutics for chronic and life-threatening human conditions including Oculopharyngeal Muscular Dystrophy (OPMD). A comprehensive overview of the Company can be found on Benitec’s website at www.benitec.com. Forward Looking Statements Except for the historical information set forth herein, the matters set forth in this press release include forward-looking statements, including statements regarding Benitec’s plans to develop and commercialize its product candidates, the timing of the initiation and completion of pre-clinical and clinical trials, the timing of patient enrollment and dosing in clinical trials, the timing of expected regulatory filings, the clinical utility and potential attributes and benefits of ddRNAi and Benitec’s product candidates, potential future out-licenses and collaborations, the intellectual property position and the ability to procure additional sources of financing, and other forward-looking statements. These forward-looking statements are based on the Company’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the FDA and other governmental authorities; the Company’s ability to protect and enforce its patents and other intellectual property rights; the Company’s dependence on its relationships with its collaboration partners and other third parties; the efficacy or safety of the Company’s products and the products of the Company’s collaboration partners; the acceptance of the Company’s products and the products of the Company’s collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; greater than expected expenses; expenses relating to litigation or strategic activities; the Company’s ability to satisfy its capital needs through increasing its revenue and obtaining additional financing, given market conditions and other factors, including our capital structure; our ability to continue as a going concern; the length of time over which the Company expects its cash and cash equivalents to be sufficient to execute on its business plan; the impact of the COVID-19 pandemic, the disease caused by the SARS-CoV-2 virus and similar events, which may adversely impact the Company’s business and pre-clinical and clinical trials; the impact of local, regional, and national and international economic conditions and events; and other risks detailed from time to time in the Company’s reports filed with the Securities and Exchange Commission. The Company disclaims any intent or obligation to update these forward-looking statements. Investor Relations Contact: Irina KofflerLifeSci Advisors, LLC (917) 734-7387ikoffler@lifesciadvisors.com

▎药明康德内容团队编辑近期，全球细胞和基因疗法（CGT）领域迎来系列进展。其中：Abeona Therapeutics开发的基因疗法prademagene zamikeracel的生物制品许可申请获得FDA的优先审评资格，用于治疗隐性营养不良性大疱性表皮松解症。亘喜生物的FasTCAR-T GC012F疗法的IND申请获得美国FDA许可，用于治疗难治性系统性红斑狼疮。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。图片来源：123RF◇Abeona Therapeutics宣布，美国FDA已接受其在研疗法pz-cel（prademagene zamikeracel，EB-101）的生物制品许可申请（BLA），并授予其优先审评资格。该疗法是一款自体、COL7A1基因校正表皮，用于治疗隐性营养不良性大疱性表皮松解症（RDEB）患者。美国FDA已设定该申请的PDUFA目标日期为2024年5月25日。该BLA申请主要获关键3期VIITAL研究以及另一项1/2a期研究的临床疗效和安全性数据支持。两项研究均显示，在大型和慢性伤口上单次应用pz-cel治疗可实现持续伤口愈合和疼痛减轻。◇亘喜生物宣布，旗下FasTCAR-T GC012F疗法的IND申请获得美国FDA许可。亘喜生物将在美国启动FasTCAR-T GC012F疗法治疗难治性系统性红斑狼疮（rSLE）的1/2期临床试验。GC012F是一款基于亘喜生物专有的FasTCAR技术平台开发的BCMA/CD19双靶点自体CAR-T细胞疗法，有望变革性地为癌症和自身免疫性疾病治疗带来快速、深入且持久的效果，并具备差异化的安全性优势。FasTCAR是亘喜生物在2017年推出的次日生产自体CAR-T细胞技术平台，旨在通过强化疗效、降低生产成本，并提升CAR-T疗法的可及性，从而显著改善患者预后。FasTCAR平台可将细胞生产周期由传统的数周时间大幅加速至次日完成，有望显著缩短患者等待期，并降低疾病进展恶化的风险。更重要的是，与传统CAR-T工艺制备的细胞相比，FasTCAR-T细胞表型更年轻，使其具备了更好的体内扩增以及更有效的肿瘤杀伤能力。◇Benitec Biopharma宣布首例患者已在基因疗法BB-301的1b/2a期临床试验中完成给药。BB-301是该公司首个采用沉默和替换方法的基因治疗候选药物，正在开发用于治疗眼咽肌营养不良相关吞咽困难。BB-301是一款利用改造的腺相关病毒（AAV9）衣壳，表达双功能转基因的基因疗法。它包括密码子优化，表达野生型PABPN1蛋白的转基因和两种针对PABPN1突变蛋白的siRNAs。两种siRNA可沉默PABPN1突变蛋白的表达，同时允许密码子优化的PABPN1转基因的表达，用具有功能的蛋白替换突变体。◇Neurogene宣布其正在进行的基因疗法NGN-401的1/2期试验中，前两名患有Rett综合征的女性儿童患者已经完成给药。迄今为止，NGN-401耐受性良好，无治疗中出现的或手术相关的严重不良事件，无转基因相关过表达毒性的迹象。NGN-401是一种在研AAV基因疗法，递送表达全长人甲基胞嘧啶结合蛋白2（MeCP2）的转基因。NGN-401利用Neurogene专有的基因调控技术，提供高度控制和一致的MeCP2表达，从而避免了与常规基因治疗相关的过表达相关毒性。在临床相关剂量的NGN-401非临床研究中，Rett综合征的主要特征得到改善，未观察到过表达毒性。◇Ferring Pharmaceuticals宣布，基因疗法Adstiladrin（nadofaragene firadenovec）在高危卡介苗（BCG）无反应性非肌层浸润性膀胱癌（NMIBC）成人患者中表现出持久疗效。3期临床试验的36个月随访数据表明，四分之一的高危、BCG无反应的NMIBC患者仍无高级别复发。同时数据显示三年总生存率为90%，超过一半的患者在36个月时未接受膀胱切除治疗。Adstiladrin是一种以非复制型腺病毒载体为基础，递送表达干扰素α-2b转基因的基因疗法。它通过导管直接注入膀胱，使膀胱壁细胞分泌大量干扰素α-2b蛋白。干扰素α-2b是机体用于抗癌的一种天然蛋白质。这种方法将膀胱壁细胞变成制造干扰素的微型工厂，增强人体自身对癌症的自然防御。◇KSQ Therapeutics公司宣布，其工程化肿瘤浸润淋巴细胞（eTIL）项目KSQ-001EX的1/2期临床研究的IND申请已经获得美国FDA的许可。KSQ-001EX由SOCS1基因被CRISPR/Cas9基因编辑失活的TIL组成。KSQ的CRISPRomics平台确定SOCS1是调控TIL抗肿瘤效力和持久性的关键基因，这一改造为KSQ-001EX在实体瘤治疗中提供了”best-in-class“潜力。这项开放标签，1/2期临床试验将在黑色素瘤、头颈部鳞状细胞癌和非小细胞肺癌患者中评估KSQ-001EX的安全性和抗癌活性。◇ASC Therapeutics宣布，其在研第二代血友病A基因疗法ASC618在1/2a期临床试验中完成首例患者给药。ASC618是一种用于治疗中重度血友病A患者的基因疗法。ASC618利用AAV载体递送的转基因，包含一个专有的B结构域缺失密码子优化的改良嵌合凝血因子VIII基因和一个肝脏特异性启动子。临床前研究中显示，这款基因疗法可以在更低的剂量下产生治疗水平的凝血因子VIII蛋白。◇uniQure宣布，该公司治疗法布里病的候选基因疗法AMT-191的IND申请获得美国FDA的许可。AMT-191通过AAV5载体递送表达α-半乳糖苷酶A（GLA）的转基因，旨在靶向肝脏并产生患者缺失的GLA蛋白。◇Carisma Therapeutics公司宣布，在研嵌合抗原受体-单核细胞疗法（CAR-单核细胞）CT-0525的IND申请获得美国FDA的许可，治疗过度表达人表皮生长因子受体2（HER2）的实体瘤。Carisma预计将在未来几个月启动1期临床试验，并在2024年上半年治疗首例患者。CT-0525是一种离体基因修饰的CAR-单核细胞疗法。在2022药明康德全球论坛上，Carisma Therapeutics的首席医学官Debora Barton博士表示，在实体瘤的微环境中，T细胞耗竭，同时巨噬细胞大量存在，因此，对于实体瘤的治疗，探索嵌合抗原受体巨噬细胞（CAR-M）是有意义的。CAR-单核细胞有可能解决用细胞疗法治疗实体瘤的挑战，包括肿瘤浸润、肿瘤微环境内的免疫抑制和抗原异质性。◇Neurona Therapeutics公司宣布，将公布正在进行的同种异体细胞疗法NRTX-1001治疗耐药性内侧颞叶癫痫（MTLE）的1/2期开放标签临床试验的最新临床数据。NRTX-1001是一种来源于人类多能干细胞的再生神经细胞疗法。完全分化的中间神经元分泌抑制性神经递质γ-氨基丁酸（GABA）。通过一次性给药，中间神经元旨在整合并支配靶神经回路，并持久沉默大脑癫痫区域的癫痫发作活动。数据显示，NRTX-1001在所有初始受试者中表现出良好的耐受性，数据安全监查委员会（DSMB）基于对第一队列安全性数据的审评做出了积极决定，允许在接受更高剂量的第二队列中对5例受试者给药。最初2例受试者继续报告治疗后1年总体平均每月癫痫发作次数减少>95%。◇TC BioPharm公司宣布，在研疗法TCB008在复发性/难治性急性髓系白血病（AML）中开展1B期临床试验的IND申请获得美国FDA的许可。TCB008是一种同种异体、未经改造的细胞疗法，由活化和扩增的γδT细胞组成。它源于健康供体的γδT细胞，大量扩增并活化之后，纯化并冷冻保存，可为患者提供一种现货型治疗手段。除了上述动态，本周细胞和基因疗法领域还有一些其它进展，限于篇幅，本文不再一一介绍。希望该领域迎来更多的新进展和突破，惠及更多患者。大家都在看作为药明康德旗下专注于细胞和基因疗法的CTDMO，药明生基致力于加速和变革基因和细胞治疗及其他高端治疗的开发、测试、生产和商业化。药明生基能够助力全球客户将更多创新疗法早日推向市场，造福病患。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Benitec Biopharma Announces First Subject Dosed in Phase 1b/2a Clinical Trial for Gene Therapy Candidate BB-301 for the Treatment of Oculopharyngeal Muscular Dystrophy. Retrieved December 1, 2023, from https://www.globenewswire.com/news-release/2023/11/30/2788463/0/en/Benitec-Biopharma-Announces-First-Subject-Dosed-in-Phase-1b-2a-Clinical-Trial-for-Gene-Therapy-Candidate-BB-301-for-the-Treatment-of-Oculopharyngeal-Muscular-Dystrophy.html [2] Neurogene Doses First Patients in Phase 1/2 Trial of NGN-401 for the Treatment of Female Pediatric Patients with Rett Syndrome. Retrieved December 1, 2023, from https://www.businesswire.com/news/home/20231130041203/en/[3] New Data Show Durable Response Following Treatment with ADSTILADRIN® (nadofaragene firadenovec-vncg). Retrieved December 1, 2023, from https://www.businesswire.com/news/home/20231129139168/en/[4] ASC Therapeutics Doses First Patient with ASC618 Second-Generation Gene Therapy for Hemophilia A. Retrieved December 1, 2023, from https://www.businesswire.com/news/home/20231128715945/en[5] uniQure Announces FDA Clearance of Investigational New Drug Application for AMT-191 Gene Therapy for Fabry Disease. Retrieved December 1, 2023, from https://www.globenewswire.com/news-release/2023/11/29/2787620/0/en/uniQure-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-AMT-191-Gene-Therapy-for-Fabry-Disease.html[6] Abeona Therapeutics Announces FDA Accepts and Grants Priority Review for Pz-cel Biologics License Application (BLA). Retrieved December 1, 2023, from https://www.globenewswire.com/news-release/2023/11/27/2786066/0/en/Abeona-Therapeutics-Announces-FDA-Accepts-and-Grants-Priority-Review-for-Pz-cel-Biologics-License-Application-BLA.html[7] Neurona Therapeutics Presents New Clinical Data from First Cohort in Ongoing Phase I/II Open-Label Trial of NRTX-1001 Cell Therapy for Drug-resistant Mesial Temporal Lobe Epilepsy (MTLE). Retrieved December 1, 2023, from https://www.globenewswire.com/news-release/2023/12/01/2789334/0/en/Neurona-Therapeutics-Presents-New-Clinical-Data-from-First-Cohort-in-Ongoing-Phase-I-II-Open-Label-Trial-of-NRTX-1001-Cell-Therapy-for-Drug-resistant-Mesial-Temporal-Lobe-Epilepsy-.html[8] Protara Therapeutics Announces Presentation of Additional Encouraging Data from Phase 1a ADVANCED-1 Trial of TARA-002 in NMIBC at the 24th Annual Meeting of the Society of Urologic Oncology. Retrieved December 1, 2023, from https://www.globenewswire.com/news-release/2023/11/30/2788580/0/en/Protara-Therapeutics-Announces-Presentation-of-Additional-Encouraging-Data-from-Phase-1a-ADVANCED-1-Trial-of-TARA-002-in-NMIBC-at-the-24th-Annual-Meeting-of-the-Society-of-Urologic.html[9] KSQ Therapeutics Announces FDA Clearance of IND Application for KSQ-001EX, a CRISPR/Cas9 Engineered Tumor Infiltrating Lymphocyte (eTIL®) Therapy. Retrieved December 1, 2023, from https://www.globenewswire.com/news-release/2023/11/29/2787601/0/en/KSQ-Therapeutics-Announces-FDA-Clearance-of-IND-Application-for-KSQ-001EX-a-CRISPR-Cas9-Engineered-Tumor-Infiltrating-Lymphocyte-eTIL-Therapy.html[10] Carisma Therapeutics Announces FDA Clearance of IND Application for CT-0525, a Novel HER2-Targeting CAR-Monocyte. Retrieved December 1, 2023, from https://www.prnewswire.com/news-releases/carisma-therapeutics-announces-fda-clearance-of-ind-application-for-ct-0525-a-novel-her2-targeting-car-monocyte-301998422.html[11] TC BioPharm Announces FDA Clearance of Phase 1B IND for TCB-008 in Acute Myeloid Leukemia. Retrieved December 1, 2023, from https://www.prnewswire.com/news-releases/tc-biopharm-announces-fda-clearance-of-phase-1b-ind-for-tcb-008-in-acute-myeloid-leukemia-301997956.html[12] Gracell Biotechnologies Announces FDA Clearance of IND Application for Phase 1/2 Clinical Trial of FasTCAR-T GC012F for the Treatment of Refractory Systemic Lupus Erythematosus. Retrieved December 1, 2023, from https://www.globenewswire.com/news-release/2023/11/27/2786133/0/en/Gracell-Biotechnologies-Announces-FDA-Clearance-of-IND-Application-for-Phase-1-2-Clinical-Trial-of-FasTCAR-T-GC012F-for-the-Treatment-of-Refractory-Systemic-Lupus-Erythematosus.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Announcement marks the initiation of the first clinical trial conducted in human subjects employing Benitec’s “Silence and Replace” DNA-directed RNA interference gene therapy platformHAYWARD, Calif., Nov. 30, 2023 (GLOBE NEWSWIRE) -- Benitec Biopharma Inc. (NASDAQ: BNTC) (“Benitec” or the “Company”), a clinical-stage, gene therapy-focused, biotechnology company developing novel genetic medicines based on its proprietary “Silence and Replace” DNA-directed RNA interference ("ddRNAi") platform, today announced the first subject has been dosed in the BB-301 Phase 1b/2a Clinical Treatment Study. BB-301 is the Company’s first gene therapy candidate employing the Silence and Replace approach and is being developed for the treatment of Oculopharyngeal Muscular Dystrophy-related Dysphagia. Dosing of the first subject marks the beginning of the 52-week follow-up period designed to facilitate conclusive evaluation of the primary and secondary endpoints of the BB-301 Phase 1b/2a Clinical Treatment Study. Interim safety and efficacy evaluations will be conducted at the end of each 90-day period following the administration of BB-301. “We are grateful to have the opportunity to begin the clinical evaluation of BB-301 and encouraged by the research and development progress made to date. We are deeply appreciative of the unwavering dedication of the clinical research team at our U.S. clinical trial site, our clinical and scientific research advisors in France, and our specialist speech language pathology research advisors in Canada, all of whom have guided the evolution of our understanding of the natural history of OPMD and our implementation of the ideal processes and procedures to facilitate the conduct of the initial clinical evaluation of BB-301,” said Jerel A. Banks, M.D., Ph.D., Executive Chairman and Chief Executive Officer of Benitec. “Today we have taken a critical step towards the clinical validation of our Silence and Replace-based approach to the management of genetically defined disorders, and our central goals remain focused on the improvement of the lives of patients suffering from OPMD.” Oculopharyngeal Muscular Dystrophy (OPMD) is a chronic, life-threatening genetic disorder affecting approximately 15,000 patients in the United States, Canada, Western Europe, and Israel. OPMD patients lose the ability to swallow liquids and solids, resulting in chronic malnutrition, aspiration, and fatal episodes of aspiration pneumonia. Currently, there are no therapeutic agents approved for the treatment of OPMD. Subjects enrolled in Benitec’s ongoing OPMD Natural History (NH) study will become eligible to roll over into the BB-301 Phase 1b/2a Clinical Treatment Study for the treatment of OPMD-related dysphagia after 6 months of baseline data collection. Following a 1-day dosing procedure for BB-301, each study subject will be evaluated for the same radiographic and clinical outcome measures as were evaluated during the NH study, including quantitative radiographic swallowing studies to facilitate objective assessments of swallowing safety, swallowing efficiency, and functional performance of the pharyngeal constrictor muscles underlying the OPMD-related dysphagia. Currently, there are 19 subjects enrolled into the NH study at the U.S. clinical trial site, with each subject having the potential to roll over into the BB-301 Phase 1b/2a Clinical Treatment Study. Interim safety and efficacy data are expected to become available from the BB-301 Phase 1b/2a Clinical Treatment Study in mid-2024. About BB-301 BB-301 is a novel, modified AAV9 capsid expressing a unique, single bifunctional construct promoting co-expression of both codon-optimized Poly-A Binding Protein Nuclear-1 (PABPN1) and two small inhibitory RNAs (siRNAs) against mutant PABPN1. The two siRNAs are modeled into microRNA backbones to silence expression of faulty mutant PABPN1, while allowing expression of the codon-optimized PABPN1 to replace the mutant with a functional version of the protein. We believe BB-301’s silence and replace mechanism is uniquely positioned for the treatment of OPMD by halting mutant expression while providing a functional replacement protein. About Benitec Biopharma Inc. Benitec Biopharma Inc. (“Benitec” or the “Company”) is a clinical-stage biotechnology company focused on the advancement of novel genetic medicines headquartered in Hayward, California. The proprietary DNA-directed RNA interference “Silence and Replace” platform combines RNA interference, or RNAi, with gene therapy to create medicines that simultaneously facilitate sustained silencing of disease-causing genes and concomitant delivery of wildtype replacement genes following a single administration of the therapeutic construct. The Company is developing Silence and Replace-based therapeutics for chronic and life-threatening human conditions including Oculopharyngeal Muscular Dystrophy (OPMD). A comprehensive overview of the Company can be found on Benitec’s website at www.benitec.com. Forward Looking Statements Except for the historical information set forth herein, the matters set forth in this press release include forward-looking statements, including statements regarding Benitec's plans to develop and commercialize its product candidates, the timing of the initiation and completion of pre-clinical and clinical trials, the timing of patient enrolment and dosing in clinical trials, the timing of expected regulatory filings, the clinical utility and potential attributes and benefits of ddRNAi and Benitec's product candidates, potential future out-licenses and collaborations, the intellectual property position and the ability to procure additional sources of financing, and other forward-looking statements. These forward-looking statements are based on the Company's current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the FDA and other governmental authorities; the Company's ability to protect and enforce its patents and other intellectual property rights; the Company's dependence on its relationships with its collaboration partners and other third parties; the efficacy or safety of the Company's products and the products of the Company's collaboration partners; the acceptance of the Company's products and the products of the Company's collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; greater than expected expenses; expenses relating to litigation or strategic activities; the Company's ability to satisfy its capital needs through increasing its revenue and obtaining additional financing, given market conditions and other factors, including our capital structure; our ability to continue as a going concern; the length of time over which the Company expects its cash and cash equivalents to be sufficient to execute on its business plan; the impact of the COVID-19 pandemic, the disease caused by the SARS-CoV-2 virus, and similar events, which may adversely impact the Company's business and pre-clinical and future clinical trials; the impact of local, regional, and national and international economic conditions and events; and other risks detailed from time to time in the Company's reports filed with the Securities and Exchange Commission. The Company disclaims any intent or obligation to update these forward-looking statements. Investor Relations Contact:Irina KofflerLifeSci AdvisorsTel: (917) 734-7387ikoffler@lifesciadvisors.com