A Prospective, Open-label, Phase 1b, Single-arm, Safety Study of an Intravitreal Application of a Recombinant Adeno-associated Virus Vector Expressing CNGA1 (AAV2.NN-CNGA1) in Patients With Retinitis Pigmentosa Due to CNGA1 Mutations

The goal of this phase 1 clinical trial is to learn about the safety and efficacy of a gene therapy, VG901, in patients with a rare disorder of the eye called Retinitis Pigmentosa. The main questions the study aims to answer are:
What is the best tolerated dose and are there any side effects, in particular any inflammatory reactions post drug administration?
Are there any early signs of efficacy on visual function?
Participants will be administered a single intravitreal dose of VG901 into the most affected eye through a syringe and followed up for a year to monitor safety and efficacy. There will be two cohorts of participants in this study. Study Cohort 1 will receive the low dose and Study Cohort 2 will receive the high dose as specified in the Protocol.

开始日期2023-09-01

申办/合作机构

ViGeneron GmbH初创企业

100 项与 VG-901 相关的临床结果

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100 项与 VG-901 相关的转化医学

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100 项与 VG-901 相关的专利（医药）

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项与 VG-901 相关的新闻（医药）

2024-04-13

·药明康德

基因编辑先驱联手打造创新递送平台，ViGeneron公司基因疗法迎来新里程碑…… | CGT周报

▎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。基因编辑先驱刘如谦和Keith Joung博士联合创建的Nvelop Therapeutics宣布正式启动，该公司基于病毒样蛋白颗粒（VLP）的递送平台有望克服目前递送载体的多重挑战，高效和细胞特异性递送广泛的治疗性载荷。ViGeneron公司宣布，在研基因疗法VG901在治疗视网膜色素变性（RP）的1b期临床试验中完成首例患者给药。新闻稿指出，VG901是首个将完整CNGA1基因递送到视网膜色素变性患者的视网膜感光细胞的临床期基因疗法。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✦———◇Obsidian Therapeutics公司日前宣布其肿瘤浸润淋巴细胞（TIL）疗法OBX-115在首个人体临床试验中的25周安全性和疗效数据。在这项治疗黑色素瘤患者的临床试验中，OBX-115达到50%的客观缓解率（ORR）和33%的完全缓解率。所有患者在接受治疗12周后肿瘤负担减轻并获得有意义的疾病控制。中位无进展生存期尚未达到，6个月时的无进展生存率为67%。OBX-115是一款自体TIL细胞疗法，通过基因工程改造表达与细胞膜结合的IL-15，有助于提高TIL细胞疗法的持久性、抗癌活性和临床安全性。◇Tr1X公司宣布，为其现货型调节性T细胞疗法TRX103递交的IND申请已经获得美国FDA的许可，用于预防接受造血干细胞移植的患者发生移植物抗宿主病。该公司计划在2024年第二季度启动预防移植物抗宿主病的1期临床试验。TRX103是一款基于健康供体捐献的CD4阳性细胞的现货型T细胞疗法。这些CD4阳性T细胞经过改造，能生成模拟Tr1调节性T细胞功能的细胞疗法。在多项临床前疾病模型中，TRX103表现出良好的耐受性和疗效，具有恢复免疫系统到健康状态的潜力。Tr1X公司正在开发TRX103治疗多种免疫和炎症性疾病。◇Ocugen公司宣布，为其在研基因疗法OCU400递交的3期临床试验IND补件已经获得美国FDA的许可，用于治疗视网膜色素变性。新闻稿指出，这是首款进入3期临床开发阶段，无需考虑RP患者携带的基因突变类型，有潜力治疗广泛患者群体的基因疗法。OCU400是一款基于视网膜核激素受体基因NR2E3的基因疗法。NR2E3基因能够调节视网膜内的多种生理功能，例如感光细胞的发育和维持、新陈代谢、光转导、炎症和细胞生存网络。OCU400通过NR2E3的驱动功能，能够重置被改变的细胞基因网络并建立体内平衡，有望改善遗传性视网膜疾病患者的视网膜健康和功能。◇Poseida Therapeutics宣布了同种异体B细胞成熟抗原（BCMA）靶向CAR-T疗法P-BCMA-ALLO1的最新1期临床试验结果。在治疗经治复发/难治性多发性骨髓瘤患者的临床试验中，P-BCMA-ALLO1达到60%的总缓解率，所有获得临床缓解的患者达到非常好的部分缓解（VGPR）水平。其中一名患者此前曾接受过BCMA靶向双特异性抗体和自体CAR-T疗法的治疗，该患者已经维持缓解超过4个月。◇ViGeneron公司宣布，在研基因疗法VG901在治疗视网膜色素变性的1b期临床试验中完成首例患者给药。新闻稿指出，VG901是首个将完整CNGA1基因递送到视网膜色素变性患者的视网膜感光细胞的临床期基因疗法。VG901是一种基因替代疗法，采用ViGeneron新一代基于AAV2的基因疗法平台vgAAV，通过玻璃体内注射（IVT）递送CNGA1基因，从而降低视网膜损伤风险。与视网膜下注射相比，这种改良后的载体提供了更方便的给药方式和更广泛的载体分布。通过与对照血清型AAV的头对头体内实验比较，显示出了更高的转导效率。此外，玻璃体内注射避免了视网膜下给药带来的视网膜损伤风险，也比脉络膜上注射的侵入性更小。相关阅读：AAV也能高效递送大型基因，ViGeneron创新基因递送技术登上《自然》子刊◇TILT Biotherapeutics公司日前公布了其在研溶瘤病毒疗法TILT-123，与重磅PD-1抑制剂Keytruda联用，治疗对含铂化疗耐药或难治性卵巢癌患者的1期临床试验最新结果。数据显示，在可评估疗效患者中，71%的患者疾病得到控制，其中一名患者获得持久的部分缓解。在接受溶瘤病毒注射和未接受溶瘤病毒注射的肿瘤中均观察到了肿瘤体积的缩小和显著免疫调节，显示局部溶瘤病毒注射可能有激发全身性免疫反应的潜力。TILT-123是一款溶瘤腺病毒，它同时表达TNF-α和IL-2，旨在改变肿瘤微环境，增强T细胞疗法的效力，包括免疫检查点抑制剂和过继性细胞疗法。———✦融资、合作、M&A✦———◇Nvelop Therapeutics宣布走出隐匿模式，旨在开发针对广泛疾病的下一代基因药物。该公司的独有递送平台有潜力高效和细胞特异性地递送广泛的治疗性载荷。Nvelop的模块化平台基于两种已经经过体内验证的递送方法。这些方法是基于基因编辑先驱刘如谦博士和Keith Joung博士实验室的研究，有望解决目前递送平台的局限性，实现基因药物的潜力，具体改善包括：递送效率：使强效疗法能够高效递送到疾病影响的多个组织，并在其中达到提供临床获益的高度活性；组织特异性：驱动针对历史上难以触达的细胞和组织的靶向体内递送；载荷多样性：允许递送类型和大小广泛的载荷，包括暂时表达的蛋白（例如，碱基编辑系统和先导编辑系统）；安全优势：载体有潜力通过优化达到完全人源化，增加其安全性，并扩大可用基因药物治疗的疾病数量。Nvelop的一种平台技术已在包括《细胞》和Nature Biotechnology在内的著名学术期刊上发表。这一技术源于刘如谦博士的实验室，在今年1月发表的论文中，其团队对病毒样蛋白颗粒进行了优化，进一步提高了VLPs的递送效率。实验结果显示，基于工程化VLPs的递送系统能够在动物体内有效递送先导编辑器，成功对小鼠视网膜细胞中的基因进行编辑。◇Century Therapeutics宣布将收购Clade Therapeutics来增强其在癌症和自身免疫性疾病领域中，基于诱导多能干细胞（iPSC）细胞疗法的管线和平台。该公司同时宣布完成6000万美元的融资，所获资金将用以支持该公司在自身免疫性疾病方面的研发活动。Century的主打项目CNTY-101是一种靶向CD19的同种异体诱导自然杀伤细胞（iNK）疗法，采用Century的Allo-Evasion平台进行6次精确基因编辑，可重复给药而无需持续进行淋巴细胞清除。CNTY-101目前正在B细胞恶性肿瘤临床试验（ELiPSE-1）中接受评估，而其用以治疗系统性红斑狼疮（SLE）的相关临床试验（CALiPSO-1）则有望于2024年上半年启动。Century计划在2024年就多个自身免疫性疾病适应症递交CNTY-101项目的监管申请。收购Clade增强了Century在同种异体iPSC衍生细胞治疗领域的布局，增强了其下一代细胞疗法平台（包括Allo-Evasion）并扩展管线。Century将获得Clade公司通过其αβiT平台所开发的三项临床前阶段项目，涵盖癌症和自身免疫性疾病。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] ViGeneron Announces First Patient Dosed in Phase 1b Clinical Trial of VG901 for the Intravitreal Treatment of Retinitis Pigmentosa. Retrieved April 12, 2024, from https://www.globenewswire.com/news-release/2024/04/10/2860550/0/en/ViGeneron-Announces-First-Patient-Dosed-in-Phase-1b-Clinical-Trial-of-VG901-for-the-Intravitreal-Treatment-of-Retinitis-Pigmentosa.html[2] Nvelop Therapeutics Launches with Dual Platforms for In Vivo Delivery of the Next Generation of Genetic Medicines. Retrieved April 12, 2024, from https://www.businesswire.com/news/home/20240409667451/en[3] Poseida Therapeutics Presents New Phase 1 Data at AACR 2024 Supporting Potential of P-BCMA-ALLO1 Allogeneic CAR-T Therapy to Benefit Broad Range of Patients with Multiple Myeloma. Retrieved April 12, 2024, from https://www.prnewswire.com/news-releases/poseida-therapeutics-presents-new-phase-1-data-at-aacr-2024-supporting-potential-of-p-bcma-allo1-allogeneic-car-t-therapy-to-benefit-broad-range-of-patients-with-multiple-myeloma-302110563.html[4] Three-Year Follow-up Data in BCG-Unresponsive NMIBC Show Durable Response to Treatment with ADSTILADRIN® (nadofaragene firadenovec-vncg) in Two Patient Cohorts. Retrieved April 12, 2024, from https://www.businesswire.com/news/home/20240408479348/en[5] Ocugen, Inc. Announces U.S. FDA Clearance of IND Amendment to Initiate OCU400 Phase 3 Clinical Trial — First Gene Therapy to Enter Phase 3 with a Broad Retinitis Pigmentosa Indication. Retrieved April 12, 2024, from https://www.globenewswire.com/news-release/2024/04/08/2859013/0/en/Ocugen-Inc-Announces-U-S-FDA-Clearance-of-IND-Amendment-to-Initiate-OCU400-Phase-3-Clinical-Trial-First-Gene-Therapy-to-Enter-Phase-3-with-a-Broad-Retinitis-Pigmentosa-Indication.html[6] Century Therapeutics Strengthens Position in Autoimmune Disease with Strategic Pipeline Expansion Supported by $60 Million Private Placement and Acquisition of Clade Therapeutics. Retrieved April 12, 2024, from https://www.globenewswire.com/news-release/2024/04/11/2861378/0/en/Century-Therapeutics-Strengthens-Position-in-Autoimmune-Disease-with-Strategic-Pipeline-Expansion-Supported-by-60-Million-Private-Placement-and-Acquisition-of-Clade-Therapeutics.html[7] Tr1X Announces FDA Clearance of First Investigational New Drug Application for TRX103, an Allogeneic Regulatory T-Cell Therapy to Treat Autoimmune Diseases. Retrieved April 12, 2024, from https://www.prnewswire.com/news-releases/tr1x-announces-fda-clearance-of-first-investigational-new-drug-application-for-trx103-an-allogeneic-regulatory-t-cell-therapy-to-treat-autoimmune-diseases-302112587.html[8] Obsidian Therapeutics Presents Positive 25-Week Median Study Follow-Up Safety and Efficacy Data from First-in-Human Study of OBX-115 in Advanced Melanoma at the American Association for Cancer Research Annual Meeting. Retrieved April 12, 2024, from https://www.businesswire.com/news/home/20240409687216/en[9] Imugene's oncolytic virotherapy VAXINIA and B cell immunotherapy HER-Vaxx featured at the AACR Annual Meeting 2024. Retrieved April 12, 2024, from https://www.globenewswire.com/news-release/2024/04/09/2860250/0/en/Imugene-s-oncolytic-virotherapy-VAXINIA-and-B-cell-immunotherapy-HER-Vaxx-featured-at-the-AACR-Annual-Meeting-2024.html[10] TILT Biotherapeutics Presents Clinical Data on TILT-123 in Combination with KEYTRUDA® (pembrolizumab) for Ovarian Cancer at AACR 2024. Retrieved April 12, 2024, from https://www.globenewswire.com/news-release/2024/04/10/2860497/0/en/TILT-Biotherapeutics-Presents-Clinical-Data-on-TILT-123-in-Combination-with-KEYTRUDA-pembrolizumab-for-Ovarian-Cancer-at-AACR-2024.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

基因疗法临床申请细胞疗法临床1期临床3期

2024-04-10

·BioSpace

ViGeneron Announces First Patient Dosed in Phase 1b Clinical Trial of VG901 for the Intravitreal Treatment of Retinitis Pigmentosa

VG901 is the first and only clinical-stage therapy designed to deliver a functional CNGA1 gene to retinal photoreceptor target cells in retinitis pigmentosa patients VG901, using ViGeneron’s proprietary next-generation technology platform vgAAV, is administered intravitreally (IVT), offering enhanced ease of delivery, broader vector distribution, and mitigating the risk of retinal damage linked with subretinal administration VG901 granted Orphan Drug Designation by FDA MUNICH, Germany, April 10, 2024 (GLOBE NEWSWIRE) -- ViGeneron GmbH, a next-generation clinical-stage gene therapy company, today announced that the first patient has been dosed in its Phase Ib clinical trial evaluating intravitreal injection of VG901 to treat retinitis pigmentosa (RP) caused by mutations in the CNGA1 gene. This milestone marks an important advance as the company continues to leverage its next-generation technology platforms to develop groundbreaking gene therapies addressing critical unmet medical needs. “By delivering a functional CNGA1 gene to retinal photoreceptor target cells, VG901 offers a therapeutic potential in addressing the genetic root cause for patients with retinitis pigmentosa affected by CNGA1 mutations,” commented Prof. Dr. Katarina Stingl, Head of the Clinic for Hereditary Retinal Degenerations in the Center for Ophthalmology and the Center for Rare Eye Diseases at the University of Tübingen, Germany, and the Principal Investigator for this trial. "We are excited to learn about the potential of this novel therapy and hope to make a meaningful difference to patients' lives.” “Dosing our first patient in the VG901 Phase Ib clinical trial is a significant step forward for the company and for the patients we aim to benefit. VG901 has also been granted FDA Orphan Drug Designation status. We look forward to progressing the clinical development of this potentially transformative therapy,” said Dr. Caroline Man Xu, ViGeneron’s Co-founder and CEO. “Not only is the Phase Ib trial designed to provide key insights into the safety and preliminary efficacy of VG901, it is also a pivotal step in validating our next generation vector platform vgAAV, which has demonstrated superior transduction efficiency and enables intravitreal delivery.” The on-going Phase Ib clinical trial is an open-label, single-arm, dose-escalation study investigating the safety, tolerability, and preliminary efficacy of an intravitreal injection of VG901, a first-in-class CNGA1 gene therapy for autosomal recessive RP. For more information on the trial, please visit clinicaltrial.gov [NCT06291935]. About Retinitis Pigmentosa (RP) Retinitis pigmentosa (RP) is a group of related eye disorders that cause progressive vision loss. RP initially presents as nighttime blindness during childhood or early adulthood, progressing to peripheral visual field loss and “tunnel vision”, central visual impairment, reduced visual acuity, and ultimately, complete blindness. Retinitis pigmentosa is the most common type of inherited retinal diseases (IRDs). It is estimated to affect 1 in 3,500 to 1 in 4,000 people in the United States and Europe, respectively. Mutations in the CNGA1 gene, encoding a subunit of CNG channels in rod photoreceptors, are reported to cause approximately 2% - 8% of autosomal recessive retinitis pigmentosa (arRP). About ViGeneron GmbH ViGeneron is dedicated to bringing gene therapy innovations to people in need. The company is advancing its proprietary, clinical-stage gene therapy pipeline to treat ophthalmic diseases, while partnering with leading biopharmaceutical players in retinal diseases, CNS, cardiovascular and other disease areas. ViGeneron’s three novel next-generation gene therapy platforms are geared towards addressing the limitations of existing adeno-associated virus (AAV)-based gene therapies. The first, the vgAAV vector platform, enables a superior transduction efficiency of target cells and is designed to overcome biological barriers, thus enabling novel, less invasive routes of administration such as intravitreal and systemic administration. The second, the REVeRT (REconstitution Via mRNA Trans-splicing) technology platform, allows for efficient reconstitution of large genes (>5kb) in any tissue which can be targeted with a given capsid. The third, the AAV Transactivation is a CRISPR-Cas–based AAV gene therapy platform that enables the regulation of one or multiple genes in vivo by increasing or inhibiting their expression. Privately-owned ViGeneron was founded in 2017 by a seasoned team with in-depth experience in AAV vector technology and clinical ophthalmic gene therapy programs and is located in Munich, Germany. For further information, please visit . ViGeneron Contact ViGeneron GmbH Dr. Caroline Man Xu Co-Founder and CEO info@vigeneron.com ViGeneron Media Contact MC Services AG Shaun Brown / Julia von Hummel phone: +49 (0)89 2102280 vigeneron@mc-services.eu

临床1期基因疗法孤儿药临床结果

2023-10-25

·药明康德

速递 | AAV也能高效递送大型基因，ViGeneron创新基因递送技术登上《自然》子刊

▎药明康德内容团队编辑今日，ViGeneron宣布在知名学术期刊《自然-通讯》（Nature Communications）上发表了一篇经同行评审的论文，展示了其基于mRNA反式剪接的专有双腺相关病毒（AAV）载体技术REVeRT的潜力。数据表明，该技术能以较高的重组效率递送大于常规AAV包装尺寸的基因，从而实现基因替代、或同时敲除和转录激活不同的基因。虽然治疗性AAV载体在当前的基因疗法中是最有效且最广泛之一使用的基因递送方法，但其小于5 kb的基因组包装能力的局限性限制了该载体用于表达大型治疗相关基因，这无疑为新型基因疗法的开发带来了重大挑战。REVeRT是一种基于AAV载体的创新灵活的双载体方法，旨在通过将基因分成两部分并包装到单独的AAV载体中，然后通过mRNA反式剪接重组来克服这一限制。根据《自然-通讯》发表的研究报告，REVeRT技术在体外和体内均得到了验证，证明了其能够高效重组大于5 kb的疾病相关基因和基因编辑模块。REVeRT技术不仅实现了目的基因的高表达，而且避免了外来蛋白的副产品生成，从而减轻了潜在的免疫原性问题。REVeRT能够灵活地选择分割位点，而且适用于各种AAV血清型和不同的给药途径，将目的基因高效地递送到各种组织和器官，包括眼睛、心脏、脑等。Stargardt病小鼠模型中，研究人员进一步证实了利用REVeRT技术能够成功实现ABCA4基因的高表达——这是一种与Stargardt病密切相关的基因。初步实验数据支持了视网膜功能的潜在改善。ViGeneron公司的联合创始人兼首席执行官徐曼博士在新闻稿中表示：“这篇同行评审论文所发表的数据证明了我们的REVeRT技术在高效递送大型基因方面的变革性潜力。我们在Stargardt项目VG801中利用REVeRT技术取得了重大进展，该项目将于明年进入临床试验阶段，同时进行的还有针对视网膜色素变性的VG901项目。这再次证明了我们致力于推进尖端基因疗法的决心，这些疗法有望改变患者的生活。”ViGeneron公司的首席商务官Markus Kalousek博士表示：“REVeRT平台使我们有能力应对一些最常见的遗传性疾病，这些疾病往往与大型基因有关。它还能实现反式激活——这是一种由CRISPR驱动的技术，具有调节遗传性和非遗传性疾病中任意大小的多个基因的潜力。我们正在积极探索各种疾病领域的战略合作伙伴关系，以加快向患者提供这些变革性的治疗方法。”大家都在看▲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] Nature Communications publication reveals highly efficient AAV delivery of large genes using ViGeneron´s REVeRT technology Retrieved October 25, 2023 from https://vigeneron.com/press/nature-communications-publication-reveals-highly-efficient-aav-delivery-of-large-genes-using-vigenerons-revert-technology/[2] Riedmayr, L.M., Hinrichsmeyer, K.S., Thalhammer, S.B. et al. mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy. Nat Commun 14, 6578 (2023). https://doi.org/10.1038/s41467-023-42386-0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

基因疗法信使RNA

100 项与 VG-901 相关的药物交易

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