Gamma amino butyric acid(Diamyd Medical AB)

▎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，多款直接送入大脑的细胞疗法和基因疗法公布积极动向：治疗帕金森病的基因疗法AB-1005的长期（18个月）耐受性良好；治疗额颞叶痴呆（FTD）患者的基因疗法AVB-101和治疗帕金森病的自体细胞疗法ANPD001均已在早期临床试验中为首例患者给药。将基因治疗与溶瘤病毒治疗结合起来的创新疗法YSCH-01在中国获批临床，有望增加数十甚至百倍的抗癌效果。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。◇ 拜耳（Bayer）公司旗下Asklepios BioPharmaceutical（AskBio）公司公布了其治疗帕金森病的在研基因疗法AB-1005的1b期临床试验结果。此次公布的结果显示，接受AB-1005治疗后的第18个月，所有11名患者均耐受良好，未发生严重不良事件，达到试验的主要目标。基于这一结果，两家公司已经启动了一项2期临床试验，预计将于今年晚些时候开始在美国、欧盟和英国招募患者。AB-1005是一种基于腺相关病毒血清型2（AAV2）载体的在研基因疗法，含有编码人胶质细胞源性神经营养因子（GDNF）的转基因。通过磁共振成像（MRI）监测的对流增强给药方式直接进行神经外科注射后，GDNF可以在大脑局部区域实现稳定和连续的表达。◇ Benitec Biopharma公司公布了其开发的用于治疗眼咽肌营养不良（Oculopharyngeal Muscular Dystrophy）的沉默和取代基因疗法BB-301在早期临床试验中的首位患者的疗效数据。此次公布的数据显示，与该研究在自然史观察导入期进行的治疗前评估相比，接受BB-301治疗后第90天时，该研究中首个患者的多种吞咽功能指标均获得了改善。安全性方面，未在接受BB-301治疗的两名受试者中观察到严重不良事件。两名受试者出现了短暂的2级胃食管反流病（即“反酸”或“烧心”）。这两名受试者在短期服用了经批准用于治疗胃食管反流病的普通处方药后，胃食管反流病都得到了缓解。▲接受BB-301治疗后第90天时，患者在所有临床结局上都有改善（图片来源：参考资料[2]）该疗法利用一种新型的、经过改良的AAV9载体，表达一种独特的、单一的双功能构建体，从而能够促进密码子优化的PABPN1基因和两个针对PABPN1突变体的siRNA的共同表达。这两个siRNA被塑造成microRNA骨架，以抑制有缺陷的PABPN1突变体的表达，同时允许表达经过密码子优化的PABPN1基因，用PABPN1蛋白的功能性版本取代突变体。◇ AviadoBio公司宣布，其旨在评估AVB-101治疗具有GRN突变的额颞叶痴呆患者的1/2期临床试验ASPIRE-FTD已完成首例患者给药。新闻稿指出，这是首次在人类身上用于治疗成人神经退行性疾病的丘脑内基因治疗。AVB-101是AviadoBio公司开发的用于治疗FTD的基因疗法。遗传性FTD约占FTD总病例的三分之一，并且与三个基因的常染色体显性突变有关，包括GRN（颗粒蛋白前体）基因。颗粒蛋白前体是一种调节大脑免疫活性的蛋白。AVB-101旨在通过AAV9载体，将一个表达颗粒蛋白前体的正常基因拷贝递送至大脑，以恢复颗粒蛋白前体的正常表达。这种疗法设计为在丘脑内给药，并利用大脑的神经网络提高载体的生物分布，实现基因的最大化广泛表达。在临床前研究中，AVB-101能够将表达颗粒蛋白前体的正常基因拷贝在大脑中广泛表达的同时，避免这一基因在血清或肝脏中出现，从而减少脱靶效应。◇ 元宋生物宣布，其溶瘤病毒1类新药“重组L-IFN腺病毒注射液（YSCH-01）”获得中国国家药品监督管理局药品审评中心（CDE）批准临床，拟用于晚期实体瘤，包括但不限于头颈部鳞癌、卵巢癌、非小细胞肺癌（NSCLC）等的治疗。该产品此前已于2023年12月在美国获批IND。根据元宋生物官方新闻稿介绍，YSCH-01是元宋生物一款基于“癌症的靶向基因-病毒治疗（CTGVT）”策略构建的溶瘤病毒产品。该策略是将基因治疗与溶瘤病毒治疗结合起来，将抗癌基因插入到溶瘤病毒中而成。这一策略的抑瘤效果有望增加数十甚至百倍的抗癌效果。此外，YSCH-01的临床前研究证实，其具有双重调控、安全性高、广谱抗癌的特点，在至少7个实体肿瘤类别上产生显著效果，表现出强大的直接溶瘤作用和远隔抗癌效果。◇ Neurona Therapeutics公司公布了其候选再生细胞疗法NRTX-1001的1/2期临床试验的新数据。此次公布的结果显示，队列1接受低剂量NRTX-1001治疗的5名受试者癫痫发作的中位数比基线减少了75%，在治疗后的六个月内，5名受试者中有4名报告癫痫发作比基线减少>50%。两名受试者在接受NRTX-1001治疗后分别接受了16个月和21个月的随访，结果显示，癫痫发作较基线持续减少＞95%，生活质量测试评分也有所提高。截至目前，所有接受治疗的受试者对NRTX-1001的耐受性都很好，神经心理学测试表明没有发现神经认知障碍。该试验中队列2的前两名受试者接受了更高剂量的NRTX-1001，目前尚未报告任何严重不良事件。NRTX-1001是一种来源于人类多能干细胞的再生神经细胞治疗候选药物，用于治疗癫痫。NRTX-1001包括分泌抑制性神经递质γ-氨基丁酸（GABA）的中间神经元。作为一次性给药疗法，该药物能够提供局部长期GABA信号通路抑制，以重新平衡和修复引起癫痫以及神经系统其他疾病过度兴奋的神经网络。接受NRTX-1001一次性治疗后患者需在第一年接受免疫抑制，目的是促进NRTX-1001的整合和长期持久性。◇ 《自然》杂志子刊Nature Communications上发表的一项关于用于增强造血干细胞移植前后T细胞重建的抗病毒细胞疗法的2期临床试验结果显示，通过静脉注射给药的病毒特异性T细胞（VST）疗法可以有效治疗免疫功能低下的儿科患者，且效果超过目前的护理标准。77名要求参加研究的患者中有75人获得了合适的VST疗法。在接受过干细胞移植的47名患者中，有40例在VST输注后1个月时有可评估的数据，其中29名取得了临床缓解。◇ Aspen Neuroscience公司宣布，其旨在评估ANPD001的安全性和耐受性的1/2a期开放标签临床试验ASSPIRO已完成首例患者给药。ANPD001是一款个体化的自体细胞疗法，将患者的皮肤细胞在体外重编程生成诱导多能干细胞（iPSCs），然后将它们分化成为多巴胺神经元前体细胞（DANPCs）。这些细胞在移植到患者大脑中后可能替代受损的多巴胺神经元。新闻稿指出，这项研究是美国首个自体iPSC衍生疗法的多中心1/2a期临床试验。◇ Artiva Biotherapeutics公司宣布，AlloNK（AB-101）与单克隆抗体联合治疗狼疮性肾炎的1期试验中的首例患者已经完成给药。AlloNK是Artiva Biotherapeutics公司开发的一种源于脐带血的非基因修饰、同种异体的在研自然杀伤（NK）细胞疗法，可增强抗体依赖的细胞毒性。AlloNK目前正被开发用于增强B细胞靶向单克隆抗体的活性，以驱动B细胞耗竭。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（可上下滑动查看）[1] AskBio presents 18-month Phase Ib trial results of AB-1005 gene therapy for patients with Parkinson’s disease. Retrieved April 17, 2024, from https://www.globenewswire.com/news-release/2024/04/16/2863581/0/en/AskBio-presents-18-month-Phase-Ib-trial-results-of-AB-1005-gene-therapy-for-patients-with-Parkinson-s-disease.html[2] Benitec Biopharma Reports Positive Interim Clinical Trial Data for First OPMD Subject Treated with BB-301 in Phase 1b/2a Study. Retrieved April 19, 2024, from https://www.globenewswire.com/news-release/2024/04/18/2865286/0/en/Benitec-Biopharma-Reports-Positive-Interim-Clinical-Trial-Data-for-First-OPMD-Subject-Treated-with-BB-301-in-Phase-1b-2a-Study.html[3] AviadoBio Announces First Patient Treated in ASPIRE-FTD Clinical Trial Evaluating AVB-101 for Frontotemporal Dementia with GRN Mutations. Retrieved April 19, 2024, from https://www.businesswire.com/news/home/20240415509017/en[4] 元宋生物再添一个临床试验批件，其创新型溶瘤病毒产品获中国CDE临床试验默示许可. Retrieved Apr 13, 2024 from https://mp.weixin.qq.com/s/tRXBRm8JNNtp-WGo76AoMA[5] Neurona Therapeutics Presents Positive Clinical Update from NRTX-1001 Cell Therapy Trial in Adults with Drug-resistant Focal Epilepsy at American Academy of Neurology (AAN) 2024 Annual Meeting. Retrieved April 17, 2024, from https://www.neuronatherapeutics.com/news/press-releases/041524/[6] Aspen Neuroscience Announces First Patient Dosed in First-in-Human Phase 1/2a Clinical Trial of Autologous Neuronal Cell Replacement Therapy for Parkinson's Disease. Retrieved April 17, 2024, from https://www.prnewswire.com/news-releases/aspen-neuroscience-announces-first-patient-dosed-in-first-in-human-phase-12a-clinical-trial-of-autologous-neuronal-cell-replacement-therapy-for-parkinsons-disease-302119216.html[7] Artiva Biotherapeutics Announces First Patient Dosed in Phase 1 Trial of AlloNK® Cell Therapy Candidate in Lupus Nephritis. Retrieved April 17, 2024, from https://www.businesswire.com/news/home/20240417656558/en/[8] Keller, M.D., Hanley, P.J., Chi, YY. et al. Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment. Nat Commun 15, 3258 (2024). https://doi.org/10.1038/s41467-024-47057-2[9] Novel cell therapy treatments offer promise to immune-compromised children. Retrieved April 17, 2024, from https://www.globenewswire.com/news-release/2024/04/18/2865558/0/en/Novel-cell-therapy-treatments-offer-promise-to-immune-compromised-children.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

STOCKHOLM, April 12, 2024 /PRNewswire/ -- Diamyd Medical's precision medicine Phase 3 trial for Type 1 Diabetes, DIAGNODE-3, has enrolled 100 patients. To date, no serious adverse events have been reported, and no patients have discontinued the trial. "This is an important milestone in our Phase 3 trial and the notable zero dropout rate confirms our insights from previous trials regarding the safety and convinience of the treatment," says Ulf Hannelius, President & CEO of Diamyd Medical. "We are deeply grateful to our participants for their continued commitment to the trial and to the dedicated staff at our participating clinics for their relentless efforts." DIAGNODE-3, being the first ever precision medicine Phase 3 trial in type 1 diabetes, is ongoing in eight European countries and in the United States. The trial specifically enrols patients that carry the genetic HLA DR3-DQ2 haplotype, a genetic subgroup of type 1 diabetes that in previous trials has been associated with positive clinical response to Diamyd® treatment. The antigen-specific immunotherapy Diamyd® was in February 2024 granted Fast Track designation by the FDA and has previously been granted Orphan Drug designation in the U.S. About DIAGNODE-3 The confirmatory Phase III trial DIAGNODE-3 (), evaluating the safety and efficacy of the antigen-specific immunotherapy Diamyd® in individuals diagnosed with Type 1 Diabetes is ongoing in the United States and in eight European countries: Sweden, Spain, the Czech Republic, the Netherlands, Germany, Poland, Hungary and Estonia. DIAGNODE-3 will enroll up to 330 individuals aged 12 to 29 years, recently diagnosed (within 6 months) with Type 1 Diabetes, who carry the HLA DR3-DQ2 haplotype, a certain genetic risk factor for Type 1 Diabetes. A further stratification for HLA haplotypes is included in order to evaluate the potential super responder group of individuals who are positive for HLA DR3-DQ2 and negative for HLA DR4-DQ8. HLA testing is well established and widely available. This patient population is based on clinical efficacy and safety results from the Phase IIa and Phase IIb trials DIAGNODE-1 and DIAGNODE-2, as well as on the large-scale meta-analysis encompassing data from more than 600 individuals from previous Phase II and Phase III trials using Diamyd®. The trial design provides a high probability to reach its co-primary endpoints of preservation of endogenous insulin producing capacity measured as stimulated C-peptide and improved blood glucose control as determined by HbA1c. DIAGNODE-3 is supported in part by funding from JDRF, the leading global type 1 diabetes research and advocacy organization. About Diamyd Medical Diamyd Medical develops precision medicine therapies for the prevention and treatment of Type 1 Diabetes and LADA (Latent Autoimmune Diabetes in Adults). Diamyd® is an antigen-specific immunomodulatory therapeutic for the preservation of endogenous insulin production that has been granted Orphan Drug Designation in the U.S. as well as Fast Track Designation (Feb-2024) by the U.S. FDA. DIAGNODE-3, a confirmatory Phase III trial is actively recruiting patients with recent-onset Type 1 Diabetes in eight European countries and in the US. Significant results have previously been shown in a large genetically predefined patient group - in a large-scale meta-analysis as well as in the Company's prospective European Phase IIb trial, where Diamyd® was administered directly into a superficial lymph node in children and young adults with recently diagnosed Type 1 Diabetes. Injections into a superficial lymphnode can be performed in minutes and is intended to optimize the immune response. A biomanufacturing facility is under development in Umeå, Sweden, for the manufacture of recombinant GAD65 protein, the active ingredient in the antigen-specific immunotherapy Diamyd®. Diamyd Medical also develops the GABA-based investigational drug Remygen® as a component in the treatments of metabolic diseases. Diamyd Medical is a major shareholder in the stem cell company NextCell Pharma AB as well as in the artificial intelligence company MainlyAI AB. Diamyd Medical's B-share is traded on Nasdaq First North Growth Market under the ticker DMYD B. FNCA Sweden AB is the Company's Certified Adviser. For further information, please contact: Ulf Hannelius, President and CEO Phone: +46 736 35 42 41 E-mail: [email protected] This information was brought to you by Cision The following files are available for download: