FIG4

感谢关注转发，欢迎学术交流回复药渡Cyber，领取文献原文请点击此处链接观看CyberSAR系统详细使用教程佛罗伦萨大学首次报道了一系列可能用于治疗奥沙利铂引起的神经性病变化合物，这些化合物能够调节人碳酸酐酶亚型（hCA）以及瞬时受体电位香草素1（TRPV1）活性。所有化合物均对参与此类病理学的主要hCA表现出有效的体外抑制活性，而从中挑选的化合物具有TRPV1中度激动作用。最有效的化合物(R)-12a、(R)-37a和两种对映异构体(R)-39a、(S)-39b的体内评估发现在神经性病变小鼠模型中均能诱导持久的镇痛效果，并在给药后30分钟发挥最大功效。图1.具有CAs抑制和TRPV1激动双重活性的化合物发现和分子优化过程基于铂的化疗（即顺铂、卡铂和奥沙利铂）用于治疗肿瘤尤其是晚期转移性癌症，如结直肠癌、卵巢癌、乳腺癌和肺癌等是有效治疗药物。然而，铂类药物在临床使用过程中存在一定的毒副作用，尤其是剂量限制性毒性、肾毒性、耳毒性、骨髓抑制和神经毒性是人们主要关注的毒副作用，通常会因为毒副作用过大，导致临床停止用药。如周围神经毒性引起感觉异常或迟钝，而后转变为慢性感觉神经毒性。此外，慢性疼痛症状会严重影响生存质量。迄今为止，尚无治疗奥沙利铂引起的神经性病变的有效治疗药物，只有非甾体类抗炎药（NSAID）和阿片类药物能够减缓疼痛。虽然引起神经性病变的病理生理学机制尚不清楚，但是很多报道认同背根神经节（DRG）神经元发生稳态功能障碍可能诱发神经性病变的原因。这种假设一致认为DRG位于中枢神经系统之外，因此不受血脑屏障保护。这种理论有一个重要的证据是接受奥沙利铂治疗的患者，通过奥沙利铂代谢物（即奥沙利铂草酸盐）螯合钙离子，其瞬时受体电位（TRP）离子通道家族（如TRPM8、TRPV1和TRPA1）中的某些亚型受到干扰，引起神经性病变症状。根据这一现象，佛罗伦萨大学开始研究TRPV1这个潜在镇痛靶点，因为它能通过触发重要的钙离子流入而参与伤害性刺激的传递。通过刺激TRPV1受体，使TRPV1受体脱敏成为一种疼痛治疗的有效策略。此前发现辣椒素或树胶脂毒素（resiniferatoxin）为TRPV1受体激动剂，文献报道辣椒素视为“分子手术刀”，会导致TRPV1离子通道开放时间延长，细胞毒性作用只明显影响表达TRPV1的感觉神经元。TRPV1部分激动剂也能有效缓解疼痛。缓解疼痛的另一类药物是TRPV1拮抗剂，如Fig1 B中的capsazepine或SB-705498。TRPV1拮抗剂虽然可以逆转疼痛，但存在高热和意外烧伤等副作用，因此TRPV1拮抗剂无法进一步开发成药。神经性病变通常与DRG神经元不受控的细胞内酸化有关，导致金属(如铂)与血红蛋白形成加合物。在同一篇文献报道中认为，由于去除主要pH缓冲系统而导致的不受控pH波动可能会通过抑制碳酸酐酶（CA, EC 4.2.1.1）亚型（即碳酸酐酶II，hCAII）而逆转。基于Potenzieri等人的开创性研究，佛罗伦萨大学的研究者尝试通过使用能够抑制金属酶并激活TRPV1受体的化合物来干预神经性病变pH失衡。除了pH影响外，当KCC2在周围神经损伤中受损时，抑制大量中枢神经系统表达的碳酸酐酶（即II、VII和XII亚型）可能会导致碳酸氢盐依赖的GABAA受体的去极化减少。设计思路佛罗伦萨大学开始利用SB-705498的强效中枢神经性系统渗透性和TRPV1选择性拮抗作用作为分子改造起始化合物，基于该化合物引入最少的官能团进行分子优化以获得具有hCA抑制活性的化合物。采取的合成策略考虑到：1、用碳酸酐酶抑制的药效团如磺酰胺替换SB-705498上的CF3取代基，同时，替换苯环上不同取代基找到同时作用两个靶点的化合物；2、研究SB-705498中苯环上的溴换成间位或对位取代，同时用其它取代基团（如NO2或H）考虑替换CF3。最后，考察改造的化合物立体异构体是否对不同碳酸酐酶亚型和TRPV1受体的亲和力有影响。碳酸酐酶抑制剂作用测试了所有合成的化合物（7a,b-22a,b，24a，25a-b, 35a-46a，37b-40b，43b-46b）hCA亚型I、II、IV、VII、IX和XIII的抑制活性具体情况如表1所示。碳酸酐酶亚型抑制活性的构效关系如下：化合物7-22a,b对细胞质hCA II抑制活性Ki的范围从12.1nM到818nM。对hCA I亲和力与亚型II类似。化合物13a的效力最低（hCA I的Ki为937.6nM）。亚型I和II观察到相同的动力学趋势。值得注意的是，与包含7-22b、25b、37-40b和43-46b的 S-构型相比，所有R-构型对映异构体（7-22a、24a、25a和35-46a）具有更强的抑制活性。其中，化合物7a在两种碳酸酐酶亚型上的效力均比其S构型对映异构体7b强近10倍。化合物11a（Ki 为37.0nM）的抗hCAI活性比化合物11b（Ki为475.8nM）强13倍。而化合物10a-b、16a,b 和20a,b观察到两种对映异构体的相反抑制趋势。与R构型相比，(S)-10b、(S)-16b和(S)-20b是更有效的hCAI和II抑制剂（即(R)-10b、(R)-16b和(R)-20b）。推测R构型和S构型之间的这种逆转活性可能是由于CF3取代基。另外，化合物13a,b和17a,b等引入大体积的取代基团消除了手性中心的影响。对于hCA II而言，在苯环上引入磺酰胺取代基系列（35-46），发现磺酰胺在硫脲衍生物37-40a,b的对位或间位取代可以增加R构型对映异构体的效力。此外，当磺酰胺处于对位（如43a和45a）时，脲基衍生物表现出相同的趋势。化合物对膜蛋白hCA IV的Ki值在微摩范围内。值得注意的是，用磺酰脲取代脲导致化合物24a的效力大幅提升至纳摩水平（Ki为36.6nM）。在磺酰脲的邻位引入一个氯原子（25a,b）效力下降20倍。几乎所有的化合物对脑相关亚型hCA VII都有强烈的抑制活性，Ki在亚纳摩水平（12b Ki达到0.9nM）。结果显示化合物对亚型VII与亚型I和II相比有不同的抑制趋势，大多数S构型对映异构体比R构型更有效。而用硫脲取代脲的化合物（7a,b和8a,b）观察到相应对映体的活性翻转。与S构型（7b，Ki为12.1nM）相比，R构型的7a（Ki为6.6nM）效力高出2倍。相反，硫脲衍生物S构型8b（Ki为2.6nM）显示出比R构型（8a，Ki为8.6nM）高3倍。卤素原子邻位似乎对S构型选择性至关重要，如衍生物11a,b和21a,b，其选择性比化合物12a,b高10倍和80倍。化合物37-46中磺酰基的取代位置在对映异构体的选择性上发挥重要作用。如在间位异构体系列中，R构型相对于S构型的增加选择性。所有化合物对肿瘤相关的hCA IX和XII亚型均有效抑制，并显示Ki值在1.3nM至971.3nM。对映异构体对两类亚型的选择性主要受苯环而不是吡啶环上的取代基影响。如表1所示结果显示化合物9、14、15、17、18和21的对映异构体在hCAI X和XII之间具有反向选择性。化合物11a,b和21a,b对hCAIX的效力，用后者的硫脲基取代前者的脲基，导致S构型选择性增加（11b比11a活性高13.9倍；21b活性比11a高52.5倍）。而对于hCA XII，R构型抑制活性更高，如化合物21a,b。观察到化合物 37-46的S构型对映异构体是最佳抑制剂，特别是衍生物38a,b显示出对映异构体超过100倍的选择性。TRPV1实验评估了所选的R构型对映异构体7a、9a-16a、18a-22a、24a、35a-46a和S构型对映异构体39b和45b测试调节TRPV1受体活性，具体结果如表2所示。尽管设计的系列化合物均源自TRPV1拮抗剂SB-705498，但从表2测试的结果说明化合物具有明显的激动作用。即使很小的化学结构修饰可能导致TRPV1活性调节中激动-拮抗作用转换。如化合物10a，37a，38a，39ab，40a，45a,b和46a表现出中等激动作用，EC50值在3.1nM到74.5μM。多数在吡啶环上引入磺酰胺化合物活性丧失。化合物10a有微弱的激动活性（10a EC50为74.5μM），当化合物12a中引入2位氯取代时，激动活性显著恢复。相反，当大多数苯环上带磺酰胺取代基时显示有激动活性，EC50值在低微摩范围内，如化合物37a和45b分别为8.0μM和3.1μM。在某些情况下，立体中心的构型并不影响活性或效力，如对映异构体39a和39b的TRPV1 EC50为12.5μM。据报道，(R)-45a和(S)-45b的效力存在构型选择性，后者的活性是前者的9倍。X射线晶体结构为了阐明化合物抑制CA的分子基础，分别以1.3Å和1.6Å分辨率测定了hCA II与对映异构体(R)-37a和(S)-37b复合物的 X 射线结构（Fig3）。电子密度图分析（支持信息（SI）中的图S1）显示抑制剂(R)-37a的密度，进入催化裂隙，与配体完全相容。正如预期的那样，磺酰胺部分直接与锌离子和Thr199残基形成氢键相互作用，从而显示出此类抑制剂的典型结合模式。此外，苯磺酰胺部分与Val121和Leu198的侧链之间建立了典型的疏水相互作用，并有助于增强活性位点内的复合物。(R)-37a硫脲基部分的近端氮原子与Thr200形成水桥。在Leu198和Pro202与主支架的疏水部分之间观察到有价值的额外疏水相互作用，其负责将整个配体粘附在活性位点的疏水区域内（Fig3 A）。与hCAII结合的第二种抑制剂(S)-37b也揭示了有趣的结构特征（Fig3 B）。首先，观察到硫脲基部分呈双构象。此外，衍生物(S)-37b的尾部也观察到了有趣的特征。事实上，吡咯烷环的S构型立构中心将该部分移动到Phe131的另一侧，与该残基发生疏水相互作用。(S)-37b尾部的这种不同位置也通过吡啶环的氮与Glu69之间的水桥以及与Ile91的疏水相互作用来稳定。两种对映体(R)-37a和(S)-37b之间的结构比较（Fig3 C）也揭示了相似的特征，例如典型的苯磺酰胺与催化锌原子和Thr199的相互作用；另一方面，立体中心能够影响两个分子的尾部构象，这两个分子占据由Phe131残基划分的两个不同的疏水口袋。然而，这种结构多样性并不显著影响两种抑制剂对该亚型的抑制等级。体内止痛验证基于体外获得的CA和TRPV1谱，佛罗伦萨大学选择了最合适的化合物来进行奥沙利铂重复治疗引起的神经病理性疼痛的体内小鼠模型。考虑的化合物包括：(i) (R)-36a和(R)-43a作为缺乏TRPV1活性的有效CA抑制剂；(ii) (R)-12a和(R)-37a，对两个靶点均有效；(iii) 两种对映异构体(R)-39a和(S)-39b，对CA II和TRPV1显示出相似的有效性。结果如Fig4所示。评估了口服给药所选化合物（浓度增加至100mg/kg）后的动物舔潜伏期体内实验。观察到与以下情况存在剂量依赖性性：对TRPV1没有任何活性的化合物(R)-36a和(R)-43a显示出剂量依赖性有效性在给药后45分钟达到峰值，随后效果迅速下降，并在75分钟时被抑制（如Fig 4所示）。(R)-12a和(R)-37a在给药后30分钟达到峰值，并且有效长达45分钟。(R)-37a的效力和活性比(R)-12a更有效。这种效应可能合理地归因于(R)-37a抑制CA II的效力超过(R)-12a（即10.4倍），也考虑到DRG神经元特别富含这种亚型。(R)-39a和(S)-39b在30和100mg/kg时显著有效，在较高剂量下完全恢复奥沙利铂过敏。基于两个对映异构体的CA II和TRPV1体外活性接近（如表1和表2所示），(S)-39a略好可能是由于不同的体内代谢过程。结论这是第一次报道了关于双靶向分子能够通过同时激活TRPV1和抑制CAs酶来缓解神经性病变的文献。通过芳香环取代、脲基和硫脲基连接体之间的生物等排转换以及立体中心的引入时对两个靶标的影响进行了初步SAR分析。合成的化合物组中存在的(R)-或(S)-立体中心似乎对两个靶标的活性没有相关影响。特别引人注目的是(R)-37a和(S)-37b（即CA II Ki分别为6.7和4.9nM）的情况，因为它们与CA II共晶结构显示分子尾部位于活性位点的酶促疏水部分，并占据由Phe131残基分开的不同亚口袋。将CA弹头磺酰胺部分引入TRPV1拮抗剂调节剂SB-705498的方法导致活性逆转至中度激动作用。观察到的分子立体中心对 TRPV1 的体外影响是多种多样的。如(R)-39a和(S)-39b（即两种化合物的EC50均为12.5μM）不会引起任何效力变化，而对于化合物45，(S)-构型的激动活性比其相应的(R)-构型（EC50）高9倍。(R)-45和(S)-45分别为29.5和3.1μM。选择最有价值的体外表现化合物（即(R)-12a、(R)-36a、(R)-37a、(R)-39a、(S)-39b和(R)-43a）探索它们对OINP体内小鼠模型。所有具有CAII或TRPV1活性的化合物均能诱导持久的镇痛效果，并在给药后30分钟发挥最大功效。相反，仅具有针对CA的活性的化合物(R)-36a和(R)-43报道了中等和较短的缓解结果，从而证明了所报告分子的TRPV1激动剂部分对生物模型的重要贡献。非常有趣的是，对映异构体(R)-39a和(S)-39b在体内模型中诱导生化反应方面明显不同，前者比其 (S)-构型更有效和持久。同时具有中等活性的TRPV1激动剂和CA强抑制剂的小分子是有效且值得开发的策略，可用于最大限度地减少神经性病变诱发的症状（如疼痛）。文章来源https://doi-org.libproxy1.nus.edu.sg/10.1021/acs.jmedchem.2c01911请点击此处链接观看CyberSAR系统详细使用教程1.药渡CyberSAR结合药物设计思想，挖掘了文献及专利报道的活性的结构，通过CyberSAR以方便快速获得研发人员兴趣靶向结构，以供开拓思路，就TRPV1激动剂举例如下：2.在靶点界面选中“化学空间”选项标签下级联“聚类结构视图”选项卡，可以将CyberSAR平台收录的文献和专利具有关于TRPV1相关实验测试活性的分子以“母核结构聚类”的形式展示。其中“绿色字体高亮”的为文献报道的体外酶、细胞活性测试实验中EC50<100nM的活性分子结构、具体实验、实验结果及实验来源。3.在靶点界面选中“化学空间”选项标签下级联“原始结构视图”选项卡，可以将CyberSAR平台收录的文献具有关于TRPV1相关实验测试活性的分子以“研发阶段时光轴”的形式展示。其中绿色字体高亮的”数据挖掘“即为潜力Hit。登录方式CyberSAR在电脑浏览器端登录网址：https://data.pharmacodia.com/cybersar/，欢迎猛烈试用。请点击此处链接观看CyberSAR系统详细使用教程如需进一步沟通，请扫码添加微信联系药渡赵博士或药渡CyberSAR沟通群。

Trial participants with Spastic Paraplegia 50 (SPG50) and Charcot-Marie-Tooth disease type 4J (CMT4J) could benefit from this joint effort to manufacture new gene therapies that utilize adeno-associated virus serotype 9 (AAV9) to deliver corrected genesSAN DIEGO, Sept. 28, 2023 (GLOBE NEWSWIRE) -- Viralgen Vector Core (Viralgen) and Elpida Therapeutics (Elpida Tx) have partnered to manufacture gene therapies for use in clinical trials sponsored by Elpida Tx involving patients living with SPG50 or CMT4J. It is anticipated that these trials will take place at various sites in North America and Europe and will explore potential safety and efficacy of the new treatments to be manufactured, as well as potential quality of life improvements. SPG50 is a rare disease caused by mutations in the adaptor protein complex-4 mu 1 subunit (AP4M1), which is a protein responsible for intracellular vesicle trafficking, specifically the sorting and transport of membrane proteins within cells. The disease symptoms of children with SPG50 begin with low muscle tone, microcephaly (small head) and epilepsy, then progress to affect the entire body, resulting in intellectual disabilities and movement/neurological abnormalities. This rare disease is known to affect only around 90 people worldwide.1 Charcot-Marie-Tooth disease type 4J (CMT4J) is an autosomal recessive, potentially severe form of CMT disease caused by mutations of the lipid phosphatase FIG4, a protein involved in the regulation of phosphoinositide lipids and membrane trafficking within cells. The same CMT4J genotype can present symptoms ranging from mild clinical signs to severe disability.2 The partnership between Viralgen and Elpida Tx is expected to enable the efficient manufacture of the adeno-associated vector serotype 9 (AAV9) based therapies for use in Elpida Tx's anticipated multi-site clinical trials. Viralgen will manufacture these therapies using its production process with the Pro10TM cell line, which is exclusively licensed from AskBio and has been found to increase scalability, performance, and yield of AAV therapies.3 Terry Pirovolakis, Founder and CEO of Elpida Tx, remarks that "Viralgen is truly an amazing partner, demonstrating their genuine commitment to advance potential therapies for impacted patients. We feel so grateful and honored to be working with such an incredible partner." About Elpida Therapeutics Elpida Tx's mission aims to address the current significant unmet medical needs of patients with ultra-rare diseases. Through leveraging scientific advancements and the now well-established safety and understanding of certain gene therapies, Elpida Tx aims to put cures in reach of families and children who desperately and urgently need them. Elpida Tx's business model focuses on partnerships that promote efficiency and the chance to treat a greater number of patients, while being self-sustaining and replicable. Elpida Tx specifically focuses on advancing programs that traditional biotech companies find difficult to bring through to completion. The company pipeline includes programs that were deprioritized by biotech companies or that did not receive biotech investment to advance due to small patient populations, but which have excellent scientific data on which to build a program and springboard the science and opportunity. Elpida Tx plans to incorporate three more CNS programs into its initial program pipeline within the next six months through an application process designed for academic institutions and foundations. About Viralgen Vector CoreViralgen is a Contract Development and Manufacturing Organization (CDMO) founded in 2017 and exists as an independently operated subsidiary of AskBio, which is wholly owned and independently operated as a subsidiary of Bayer AG. As a manufacturer of Current Good Manufacturing Practice (cGMP) certified AAV, Viralgen offers the Pro10™ based suspension manufacturing platform, a technology licensed from AskBio and developed by Chief Technical Officer Josh Grieger, PhD, and Co-Founder R. Jude Samulski, PhD, at University of North Carolina. The Pro10™ platform has been found to increase scalability, performance, and yield of AAV therapies 3. Located in Spain, in the Gipuzkoa Science and Technology Park, Viralgen produces AAV gene therapy treatments for pharmaceutical and biotech companies with the aim of accelerating the delivery of new treatments that may improve patients' lives. The company's clinical facilities have four cGMP manufacturing suites, with 250-liter and 500-liter bioreactors. In 2020, Viralgen expanded within the Scientific Park by constructing a new building with three modules for large-scale commercial manufacturing. Each module of the state-of-the-art space includes three cGMP suites with a manufacturing capacity of >2,000 liters. The first module, which includes a suite dedicated to fully automated fill and finish operations, has received cGMP certification by the Spanish Agency for Medicines and Medical Devices (AEMPS) as part of the EMA network. For more information, visit viralgenvc.com. References:1 J Clin Invest. 2023 May 15; 133(10): e170226. 10.1172/JCI1702262 Brain. 2011 Jul; 134(7): 1959-1971. 10.1093/brain/awr1483 Mol Ther. 2016 Feb;24(2):287-297. doi: 10.1038/mt.2015.187. Epub 2015 Oct 6. For more information and interviews, please contact:Priscilla Assumpçãopriscilla@sg-branding.com This information is provided by Reach, the non-regulatory press release distribution service of RNS, part of the London Stock Exchange. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact rns@lseg.com or visit www.rns.com.

Viralgen Vector Core and Elpida Therapeutics partner to manufacture gene therapy medicines for anticipated Spastic Paraplegia 50 (SPG50) and Charcot-Marie-Tooth disease type 4J (CMT4J) clinical trials Trial participants with Spastic Paraplegia 50 (SPG50) and Charcot-Marie-Tooth disease type 4J (CMT4J) could benefit from this joint effort to manufacture new gene therapies that utilize adeno-associated virus serotype 9 (AAV9) to deliver corrected genes SAN SEBASTIAN, SPAIN / ACCESSWIRE / September 28, 2023 / Viralgen Vector Core (Viralgen) and Elpida Therapeutics (Elpida Tx) have partnered to manufacture gene therapies for use in clinical trials sponsored by Elpida Tx involving patients living with SPG50 or CMT4J. It is anticipated that these trials will take place at various sites in North America and Europe and will explore potential safety and efficacy of the new treatments to be manufactured, as well as potential quality of life improvements. SPG50 is a rare disease caused by mutations in the adaptor protein complex-4 mu 1 subunit (AP4M1), which is a protein responsible for intracellular vesicle trafficking, specifically the sorting and transport of membrane proteins within cells. The disease symptoms of children with SPG50 begin with low muscle tone, microcephaly (small head) and epilepsy, then progress to affect the entire body, resulting in intellectual disabilities and movement/neurological abnormalities. This rare disease is known to affect only around 90 people worldwide.1 Charcot-Marie-Tooth disease type 4J (CMT4J) is an autosomal recessive, potentially severe form of CMT disease caused by mutations of the lipid phosphatase FIG4, a protein involved in the regulation of phosphoinositide lipids and membrane trafficking within cells. The same CMT4J genotype can present symptoms ranging from mild clinical signs to severe disability.2 The partnership between Viralgen and Elpida Tx is expected to enable the efficient manufacture of the adeno-associated vector serotype 9 (AAV9) based therapies for use in Elpida Tx's anticipated multi-site clinical trials. Viralgen will manufacture these therapies using its production process with the Pro10TM cell line, which is exclusively licensed from AskBio and has been found to increase scalability, performance, and yield of AAV therapies.3 Terry Pirovolakis, Founder and CEO of Elpida Tx, remarks that "Viralgen is truly an amazing partner, demonstrating their genuine commitment to advance potential therapies for impacted patients. We feel so grateful and honored to be working with such an incredible partner." About Elpida Therapeutics Elpida Tx' s mission aims to address the current significant unmet medical needs of patients with ultra-rare diseases. Through leveraging scientific advancements and the now well-established safety and understanding of certain gene therapies, Elpida Tx aims to put cures in reach of families and children who desperately and urgently need them. Elpida Tx's business model focuses on partnerships that promote efficiency and the chance to treat a greater number of patients, while being self-sustaining and replicable. Elpida Tx specifically focuses on advancing programs that traditional biotech companies find difficult to bring through to completion. The company pipeline includes programs that were deprioritized by biotech companies or that did not receive biotech investment to advance due to small patient populations, but which have excellent scientific data on which to build a program and springboard the science and opportunity. Elpida Tx plans to incorporate three more CNS programs into its initial program pipeline within the next six months through an application process designed for academic institutions and foundations. About Viralgen Vector Core Viralgen is a Contract Development and Manufacturing Organization (CDMO) founded in 2017 and exists as an independently operated subsidiary of AskBio, which is wholly owned and independently operated as a subsidiary of Bayer AG. As a manufacturer of Current Good Manufacturing Practice (cGMP) certified AAV, Viralgen offers the Pro10™ based suspension manufacturing platform, a technology licensed from AskBio and developed by Chief Technical Officer Josh Grieger, PhD, and Co-Founder R. Jude Samulski, PhD, at University of North Carolina. The Pro10™ platform has been found to increase scalability, performance, and yield of AAV therapies 3. Located in Spain, in the Gipuzkoa Science and Technology Park, Viralgen produces AAV gene therapy treatments for pharmaceutical and biotech companies with the aim of accelerating the delivery of new treatments that may improve patients' lives. The company's clinical facilities have four cGMP manufacturing suites, with 250-liter and 500-liter bioreactors. In 2020, Viralgen expanded within the Scientific Park by constructing a new building with three modules for large-scale commercial manufacturing. Each module of the state-of-the-art space includes three cGMP suites with a manufacturing capacity of >2,000 liters. The first module, which includes a suite dedicated to fully automated fill and finish operations, has received cGMP certification by the Spanish Agency for Medicines and Medical Devices (AEMPS) as part of the EMA network. For more information, visit viralgenvc.com. References: 1 J Clin Invest. 2023 May 15; 133(10): e170226. 10.1172/JCI170226 2 Brain. 2011 Jul; 134(7): 1959-1971. 10.1093/brain/awr148 3 Mol Ther. 2016 Feb;24(2):287-297. doi: 10.1038/mt.2015.187. Epub 2015 Oct 6. For more information and interviews, please contact: Priscilla Assumpção priscilla@sg-branding.com This information is provided by Reach, the non-regulatory press release distribution service of RNS, part of the London Stock Exchange. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact rns@lseg.com or visit . SOURCE: Viralgen Vector Core View source version on accesswire.com: