ATSN-101

DURHAM, N.C., Jan. 16, 2024 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) designation to ATSN-101, the company’s investigational gene therapy being evaluated in an ongoing Phase I/II clinical trial in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1). The FDA previously granted Regenerative Medicine Advanced Therapy (RMAT) designation and orphan drug designation to ATSN-101 for the treatment of LCA1. RPD designation is granted by the FDA for serious or life-threatening diseases which affect fewer than 200,000 people in the United States and in which the serious or life-threatening manifestations primarily affect individuals less than 18 years of age. If a Biologics License Application for ATSN-101 for the treatment of LCA1 is approved by the FDA, Atsena may be eligible to receive a Priority Review Voucher that can be redeemed to receive a priority review for any subsequent marketing application or may be sold or transferred. “Rare Pediatric Disease designation is a significant milestone for our LCA1 program as we explore options to advance ATSN-101 into a pivotal clinical trial,” said Patrick Ritschel, MBA, Chief Executive Officer of Atsena Therapeutics. “The FDA designations that have been granted to ATSN-101 not only emphasize the tremendous need for a treatment for patients with LCA1, but also the potential for our subretinal gene therapy to be a major advance in reversing pediatric blindness.” Positive 12-month safety and efficacy data from the company’s ongoing Phase I/II clinical trial of ATSN-101 will be presented at the 47th Annual Macula Society Meeting, which is being held February 7-10, 2024, in Palm Springs, CA. ATSN-101 has demonstrated clinically meaningful improvements in vision at the highest dose and is well-tolerated 12 months post-treatment. Details of the presentation are as follows: Title: Twelve-month safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1) Session: Inherited Retinal Dystrophy I (Treatment Trials) Date and Time: Wednesday, February 7, 2024, 6:04 p.m. PST Presenter: Christine Nichols Kay, MD About GUCY2D-associated Leber congenital amaurosis (LCA1) LCA1 is a monogenic eye disease that disrupts the function of the retina. It is caused by mutations in the GUCY2D gene and results in early and severe vision impairment or blindness. GUCY2D-LCA1 is one of the most common forms of LCA, affecting roughly 20 percent of patients who live with this group of inherited retinal diseases. There are currently no approved treatments for LCA1. About Atsena Therapeutics Atsena Therapeutics is a clinical-stage gene therapy company developing novel treatments for inherited forms of blindness. The company has two clinical-stage programs, ATSN-201 for X-linked retinoschisis (XLRS) and ATSN-101 for GUCY2D-associated Leber congenital amaurosis (LCA1). ATSN-201, which leverages the company’s novel spreading capsid AAV.SPR, is being evaluated in XLRS patients in a Phase I/II clinical trial known as the LIGHTHOUSE study. The company’s additional proprietary asset is ATSN-301, a dual AAV vector-based gene therapy to prevent blindness from MYO7A-associated Usher syndrome (USH1B). Interim safety and efficacy data from the company’s ongoing Phase I/II clinical trial in patients with LCA1 have demonstrated ATSN-101 is well tolerated and clinically meaningful improvements in vision were observed 12 months post-treatment. Founded by ocular gene therapy pioneers Dr. Shannon Boye and Sanford Boye of the University of Florida, Atsena is based in North Carolina’s Research Triangle, an environment rich in gene therapy expertise. For more information, please visit atsenatx.com. Media Contact: Tony Plohoros 6 Degrees (908) 591-2839 tplohoros@6degreespr.com Business Contact: info@atsenatx.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：Vertex Pharmaceuticals和CRISPR Therapeutics公司联合开发的CRISPR基因编辑疗法Casgevy获得FDA批准，治疗镰刀型细胞贫血病（SCD）患者。bluebird bio公司开发的基因疗法Lyfgenia也在同日获得FDA的批准治疗这一患者群体。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———✦研发进展✦———◇美国FDA宣布，批准Vertex Pharmaceuticals和CRISPR Therapeutics联合开发的CRISPR/Cas9基因编辑疗法Casgevy（exagamglogene autotemcel，exa-cel）上市，用于治疗12岁及以上患有复发性血管闭塞危象（VOC）的镰刀型细胞贫血病患者。根据新闻稿，这是FDA批准的首款CRISPR基因编辑疗法。在Casgevy用以治疗SCD的全球性临床试验中，试验达到了主要终点，即在24个月随访期内至少连续12个月无严重VOC发作。共44例患者接受Casgevy治疗。在随访时间足够可评估的31例患者中，29例（93.5%）达到此指标，显示Casgevy具有一次治疗，提供功能性治愈的潜力。Casgevy是一款自体细胞疗法，它利用CRISPR/Cas9基因编辑系统，在体外对来自患者的造血干细胞进行改造，使血红细胞生产高水平的胎儿血红蛋白（HbF），有可能减少镰刀型细胞贫血病患者的疼痛和使人衰弱的血管闭塞性危象。◇FDA批准了bluebird bio开发的基因疗法Lyfgenia（lovotibeglogene autotemcel，lovo-cel）的生物制品许可申请（BLA），用于治疗12岁及以上患有SCD且有血管闭塞事件（VOE）史的患者。据FDA新闻稿，Lyfgenia和同时获得批准的Casgevy是用于治疗12岁及以上SCD患者的首批获得批准的细胞和基因疗法，这代表了一项重要的里程碑式进展。Lyfgenia的安全性和有效性基于对12至50岁镰刀型细胞贫血病和VOE病史患者进行的一项为期24个月的单臂多中心研究的数据分析。根据患者在接受Lyfgenia输注后6至18个月内达成VOE完全消退（VOE-CR）来评估有效性。在此期间，32例患者中有28名（88%）达到了VOE-CR。Lyfgenia是一种用于治疗SCD的一次性基因疗法，其设计目的是将改良形式的β-珠蛋白基因（βA-T87Q珠蛋白基因）的功能拷贝添加到患者自身的造血干细胞中，从而降低镰状血红蛋白（HbS）的比例，目标是减少镰状红细胞、溶血和其他并发症。◇Sana Biotechnology宣布在Blood杂志上发表了一篇摘要，提供了正在进行的1期临床试验ARDENT中首位患者在最低剂量下接受SC291治疗的初步临床数据。SC291是一种低免疫（HIP）同种异体CD19靶向CAR-T细胞疗法。SC291显示出良好的安全性和耐受性，能够规避免疫检测，并在这名慢性淋巴细胞性白血病（CLL）患者中达成了部分缓解。Sana公司的低免疫技术包括扰乱主要组织相容性（MHC）I类和II类蛋白表达，使细胞能够规避适应性免疫系统，该系统包括抗体和T细胞反应；以及过度表达CD47以规避先天性免疫细胞系统，特别是巨噬细胞和自然杀伤（NK）细胞。◇科济药业宣布，其靶向GPRC5D的自体CAR-T细胞候选疗法的IND申请已经获得美国FDA的许可，用于治疗复发/难治性多发性骨髓瘤或复发/难治性原发性浆细胞白血病患者。CT071通过科济药业专有的CARcelerate技术平台生产，可将生产时间缩短至2天以内，从而制造出比传统生产方法更年轻、更健康、可能更强效的CAR-T细胞。生产效率的提升也进一步增强供应产能、降低生产成本，并提高患者对产品的可及性。◇Century Therapeutics宣布，其同种异体NK细胞疗法CNTY-101的IND申请已经获得美国FDA的许可，将在1期临床试验中用于至少两种标准免疫抑制疗法失败的中度至重度系统性红斑狼疮（SLE）患者。CNTY-101是一种同种异体、由诱导多能干细胞（iPSC）分化制造的“现货型”NK细胞候选疗法。CNTY-101通过使用CRISPR基因编辑技术，在特定位点上进行了6次基因编辑。包括三个Allo-Evasion编辑，并导入表达IL-15、靶向CD19的CAR，以及一个安全开关的转基因。◇Vittoria Biotherapeutics宣布，其基因编辑的自体CAR-T细胞疗法VIPER-101的IND申请已获得美国FDA的许可，将启动1期临床试验用于治疗复发或难治性T细胞淋巴瘤患者。VIPER-101是一种自体、删除CD5的CAR-T疗法，采用Vittoria的专有细胞疗法工程和制造平台Senza5生产。CD5是一个泛T细胞生物标志物，也调节免疫抑制信号通路，然而，传统针对T细胞恶性肿瘤的CD5靶向CAR-T细胞疗法可能引发对T细胞疗法本身的杀伤，降低治疗效果。VIPER-101独特的设计可以避免细胞受损并发挥规避CD5抑制信号通路的益处。◇Atsena Therapeutics公布了在研基因疗法ATSN-101正在进行中的1/2期临床试验的12个月安全性和有效性积极数据。这一基因疗法用于治疗与GUCY2D相关的Leber先天性黑蒙（LCA1）。在治疗后12个月，ATSN-101在最高剂量下展现了临床上有意义的视力改善，并且没有出现严重的治疗后出现的不良事件。◇Solid Biosciences宣布，美国FDA授予该公司下一代杜氏肌营养不良症（DMD）在研基因疗法SGT-003快速通道资格。SGT-003使用一种专有、理性设计的衣壳（AAV-SLB101）来递送编码微抗肌萎缩蛋白的DNA序列，包含R16-R17 nNOS结合域。临床前数据表明，这对于患者的肌肉功能和治疗效益的持久性都很重要。———✦合作、融资、M&A✦———◇Kamau Therapeutics宣布走出隐匿模式。该公司与Graphite Bio达成协议，Kamau获得了收购Graphite Bio所有基因编辑资产的选择权，包括一个使用同源定向修复（HDR）和CRISPR基因编辑，精确修复DNA的平台技术。该公司的主打疗法Nula-cel是一种造血干细胞疗法，旨在通过精确修正引起镰状血红蛋白的突变来恢复正常的成人血红蛋白，这可能为镰刀型细胞贫血病患者提供治愈方法。该疗法已在首位接受治疗的SCD患者中建立了概念验证。这些数据将在12月11日在2023年美国血液学会（ASH）年会的海报展示环节中展出。◇Eligo Bioscience宣布成功完成了由赛诺菲创投领投的3000万美元B轮融资。Eligo专注于利用噬菌体衣壳，将基因疗法和基因编辑疗法递送到微生物组中。这一技术扩大了可解决的遗传靶点范围。通过在人类微生物组内进行精确的遗传学改造，这种独特的方法有望根本改变许多慢性病和危及生命的疾病的发展过程。这些疾病由细菌基因的表达触发或驱动。◇西雅图儿童医院宣布成立BrainChild Bio公司，以加速CAR-T细胞疗法在中枢神经系统（CNS）肿瘤中的进展。BrainChild Bio将获得西雅图儿童医院开发的治疗CNS肿瘤的新型CAR-T技术的独家许可。BrainChild Bio将通过推进下一代CAR-T细胞疗法平台，优化CNS肿瘤的CAR-T细胞疗法应用。该平台整合了包括多重靶点和增强效力控制在内的合成技术。这种多维度方法包括：（i）单一CAR-T细胞疗法中靶向多重靶点以防止肿瘤逃逸；（ii）新型转基因以提高效力，仅在肿瘤环境中激活；（iii）开关技术以直接在肿瘤内控制CAR-T细胞；（iv）CAR-T设计和制造工艺。这些技术多年来在西雅图儿童医院得到验证；以及（v）新型CAR-T细胞直接注入大脑的给药方式，最小化系统毒性，并能够定期重复给药以确保CAR-T细胞的持久存在和疗效。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] Kamau Therapeutics Emerges from Stealth With Clinical-Stage Novel Gene Correction Technology Targeting Life-Threatening Genetic Diseases. Retrieved December 8, 2023, from https://www.businesswire.com/news/home/20231207959079/en[2] Solid Biosciences Receives FDA Fast Track Designation for Duchenne Muscular Dystrophy Gene Therapy SGT-003. Retrieved December 8, 2023, from https://www.globenewswire.com/news-release/2023/12/07/2792478/0/en/Solid-Biosciences-Receives-FDA-Fast-Track-Designation-for-Duchenne-Muscular-Dystrophy-Gene-Therapy-SGT-003.html[3] Seattle Children's launches BrainChild Bio to accelerate CAR T-cell therapies for children with brain tumors. Retrieved December 8, 2023, from https://www.businesswire.com/news/home/20231205267194/en[4] FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. Retrieved December 8, 2023, from https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease[5] Eligo Bioscience Raises $30 Million To Write a Novel Chapter for Genetic Medicines. Retrieved December 8, 2023, from https://www.businesswire.com/news/home/20231205514642/en[6] Atsena Therapeutics Announces Positive 12-month Safety and Efficacy Data from Ongoing Phase I/II Clinical Trial of ATSN-101 in Patients with Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D (LCA1). Retrieved December 8, 2023, from https://www.globenewswire.com/news-release/2023/12/04/2789910/0/en/Atsena-Therapeutics-Announces-Positive-12-month-Safety-and-Efficacy-Data-from-Ongoing-Phase-I-II-Clinical-Trial-of-ATSN-101-in-Patients-with-Leber-Congenital-Amaurosis-Caused-by-Bi.html[7] AbelZeta Pharma Announces Agreement with AstraZeneca to Co-Develop a novel Glypican 3 (GPC3) Armored CAR-T Therapy in China. Retrieved December 8, 2023, from https://www.prnewswire.com/news-releases/abelzeta-pharma-announces-agreement-with-astrazeneca-to-co-develop-a-novel-glypican-3-gpc3-armored-car-t-therapy-in-china-302008822.html[8] Vittoria Biotherapeutics Announces FDA Clearance of IND Application for VIPER-101 to Treat T-Cell Lymphoma. Retrieved December 8, 2023, from https://www.globenewswire.com/news-release/2023/12/07/2792443/0/en/Vittoria-Biotherapeutics-Announces-FDA-Clearance-of-IND-Application-for-VIPER-101-to-Treat-T-Cell-Lymphoma.html[9] Century Therapeutics Receives FDA Clearance of IND Application for CNTY-101 in Systemic Lupus Erythematosus. Retrieved December 8, 2023, from https://www.globenewswire.com/news-release/2023/12/06/2791671/0/en/Century-Therapeutics-Receives-FDA-Clearance-of-IND-Application-for-CNTY-101-in-Systemic-Lupus-Erythematosus.html[10] CARsgen's CT071 Received IND Clearance from the FDA for Treating Relapsed/Refractory Multiple Myeloma or Relapsed/Refractory Primary Plasma Cell Leukemia. Retrieved December 8, 2023, from https://www.prnewswire.com/news-releases/carsgens-ct071-received-ind-clearance-from-the-fda-for-treating-relapsedrefractory-multiple-myeloma-or-relapsedrefractory-primary-plasma-cell-leukemia-302004156.html[11] Sana Biotechnology Publishes Early Clinical Data Showing that SC291, a CD19-directed Allogeneic CAR T Therapy, Evades Immune Detection in Presence of Intact Immune System. Retrieved December 8, 2023, from https://www.globenewswire.com/news-release/2023/12/01/2789534/0/en/Sana-Biotechnology-Publishes-Early-Clinical-Data-Showing-that-SC291-a-CD19-directed-Allogeneic-CAR-T-Therapy-Evades-Immune-Detection-in-Presence-of-Intact-Immune-System.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