Lenadogene nolparvovec

French medicines agency ANSM and Ethics Committee authorize the dose-ranging study investigating two doses of candidate product for the treatment of ND4 -LHON. Approval of the study protocol will support the ongoing review of the named patient early access program (AAC) in France. The Phase II study is expected to start in January 2026. PARIS--(BUSINESS WIRE)--Regulatory News: GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that the French medicines safety agency ANSM (Agence nationale de sécurité du médicament et des produits de santé) has authorized the dose-ranging study REVISE, which will investigate the efficacy and safety of two dose levels of the Company’s candidate gene therapy GS010/LUMEVOQ®. The study had been requested by the agency during discussions with the Company about a named patient early access program for the candidate product, which is in clinical development for the treatment of vision loss due to Leber Hereditary Optic Neuropathy (LHON) caused by a mutated ND4 mitochondrial gene.1 Regulatory approval was granted after the ANSM assessed the GS010/LUMEVOQ® quality dossier and clinical aspects of REVISE. The study also received approval from the Ethics Committee. The regulatory approval of REVISE will support the ongoing review of GenSight Biologics’ application for the French named patient early access program (AAC) by the ANSM. REVISE is an open-label, single center, Phase II study with a target enrollment of 14 patients. The patients must all have confirmed mutations in the ND4 gene and must have 6 months to 1.5 years of vision loss at the date of treatment. Two (2) clinical doses will be investigated in the trial, with patients distributed equally over the two doses. Efficacy, as measured by the change in Best Corrected Visual Acuity (BCVA), 1.5 years post-treatment versus baseline, is the primary endpoint in REVISE. The study is expected to begin in January 2026. Company Prepares for Strategic Priorities in 2026 While the AAC application is under review, GenSight Biologics is moving forward according to target timelines with the final stages of the technology transfer to its new manufacturing partner and with the preparations to finalize the protocol for the Phase III study. In parallel, the Company is pursuing opportunities to out-license GS010 in markets outside the USA and Europe, while exploring paid Early Access Programs worldwide. About Leber Hereditary Optic Neuropathy (LHON) LHON is a rare, maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells, which results in precipitous and usually irreversible vision loss and typically leads to legal blindness. The ND4 mitochondrial mutation is the most common of the mutations that cause LHON and is associated with the worst prognosis among the leading mutations. About GenSight Biologics GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics’ pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics’ lead product candidate, GS010 (lenadogene nolparvovec) is in Phase III in Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease that leads to irreversible blindness in teens and young adults. GS010 is currently in clinical development, has not to date been granted marketing authorization in France or any other jurisdiction, and is therefore not available commercially. Using its gene therapy-based approach, GenSight Biologics’ product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery. About GS010/LUMEVOQ® (lenadogene nolparvovec) GS010/LUMEVOQ® (lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which is then shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. GS010/LUMEVOQ® (lenadogene nolparvovec) is in Phase III of its clinical development. It has not been granted marketing authorization in any country and is not available commercially. 1 GS010/LUMEVOQ has not been granted marketing authorization in any country and is not commercially available.

GenSight Biologics 是一家临床阶段的生物技术公司，致力于发现和开发治疗神经退行性视网膜疾病和中枢神经系统疾病的新型疗法。 这家总部位于伦敦的生物技术公司利用两个核心技术平台——线粒体靶向序列（MTS：Mitochondrial Targeting Sequence）和用于治疗视网膜色素变性的光遗传学技术——来帮助患有严重退行性视网膜疾病的患者保留或恢复视力。 网址：https://www.gensight-biologics.com/ （MTS：Mitochondrial Targeting Sequence） 线粒体靶向序列（MTS）是一项能够将核信使RNA直接运送至线粒体表面，并将新合成的蛋白质导入线粒体基质的技术，从而恢复线粒体功能。 药物研发管线 GenSight 拥有两种用于治疗威胁视力的退行性视网膜疾病的主要候选产品，同时还有针对眼科和神经退行性疾病的临床前开发产品。 LHON-ND4 LHON-ND4 是一种用于治疗莱伯遗传性视神经病变（Leber Hereditary Optic Neuropathy, LHON）的药物。ND4 基因通常位于线粒体中，并在其中合成 ND4 蛋白。GS010 通过其专有的线粒体靶向序列（MTS），使得线粒体基因 ND4 能够在细胞核中进行"异位表达"，并将信使 RNA 从细胞核直接运送到线粒体外膜。在那里，ND4 蛋白被合成并整合到线粒体中。随后，野生型 ND4 蛋白整合到呼吸链复合体 I 中，从而弥补其功能缺陷。 该药物目前正在美国和欧盟进行III 期临床试验。ClinicalTrials.gov 标识符：NCT03293524 LUMEVOQ GenSight Biologics 正在开发 LUMEVOQ（GS010），这是一种能够使线粒体蛋白 ND4 在细胞核中表达并被运送到线粒体的疗法。这种将线粒体 DNA 转移到受到更好保护的细胞核中的概念，是对抗衰老标志之一——线粒体功能障碍的关键方法。该公司已将 LUMEVOQ 推进到多项针对 LHON 治疗的 III 期临床试验中，LHON 是一种导致失明的疾病。 该公司过去的临床试验曾遇到一些问题，因为当时每位患者只治疗单眼以测试GS010 的疗效，另一只未治疗的眼则作为对照组。问题在于，施用这种疗法似乎不仅影响了治疗眼，也影响了未治疗眼，导致实验组和对照组之间缺乏差异——从而可能使得一种有效的疗法看起来无效。 2020 年 12 月，III 期 REVERSE 临床试验取得成功，这标志着线粒体基因疗法在人类身上成为现实。 研究人员报告称，到研究第96 周时，25 名参与者的至少一只眼睛的最佳矫正视力（BCVA）与治疗前记录的基线相比有显著改善。37 名参与者中有 29 名双眼视力均有所改善。他们发现，接受治疗后，眼睛恢复到 20/200 视力或更好的可能性提高了约三倍。 2021 年 6 月，GenSight 报告了 LUMEVOQ 在 III 期 REFLECT 临床试验中，治疗后 78 周的关键疗效和安全性结果。结果显示，与单眼注射相比，双侧玻璃体内注射该基因疗法能带来更好的 BCVA 改善。 2021 年 9 月，公布了 RESCUE 和 REVERSE III 期临床试验的长期随访结果，显示在治疗后 2 至 3 年间，BCVA 持续改善。 LUMEVOQ 已在法国获得临时使用许可，并预计在 2022 年上半年获得欧盟的上市许可。 研究人员也有兴趣使用相同的方法治疗其他线粒体疾病。 GenSight 还在开发 GS030，这是一种使视网膜细胞能够检测光线的基因疗法，目前正处于 I/II 期剂量递增研究中。 GS030 GS030 是两个部分的独特组合。第一部分是包含光敏蛋白基因的基因疗法，使用一种经过特殊修饰的病毒 AAV2 7m8 进行递送。第二部分是一副特殊的护目镜，用于刺激已被基因疗法改变的视网膜细胞。该护目镜使用特定类型的光将图像投射到视网膜上。这种方法被称为光遗传学，涉及将光敏蛋白的基因插入细胞，使这些细胞能够对光做出反应。 GS030 使用一种生物工程病毒，将这种光敏蛋白的基因导入视网膜中的靶细胞，即视网膜神经节细胞（RGCs）。这使得这些细胞对光敏感，无论最初导致它们损伤的基因突变是什么。然而，这些被改变的细胞对光的敏感度不如正常的视网膜细胞，因此在没有特殊护目镜的情况下，可能无法实现正常的日光视力。这些护目镜通过捕捉视觉信息并增强传递给视网膜中被改变细胞的光信号来工作，使这些细胞能够更接近正常细胞的功能。GS030 正在被测试作为视网膜色素变性的治疗方法。 使命 我们的使命是将基因治疗领域的科学进步转化为创新疗法，用于治疗眼部和中枢神经系统的严重退行性疾病。 end ●【科学逆龄】全球抗衰新药全解析：(1) 告别“一治多伤”：科学家找到调控TGF-β的精准钥匙，纤维化治疗迎来破局 ●【科学逆龄】全球抗衰新药全解析：(2)瞄准“衰老毒素”：这家药企正在清除导致心衰、痴呆的体内垃圾 ●【科学逆龄】全球抗衰新药全解析：(3)我们基因组里潜伏的“敌人”被锁定了！科学家用它来对抗神经退行与衰老 ●【科学逆龄】全球抗衰新药全解析：(4)下一个爆款何在？深扒英矽智能：看AI如何“凭空”造出10余款新药 生理年龄（甲基化年龄）检测 甲基化时钟，能够通过分析DNA甲基化模式来估算个体的生物学年龄(甲基化年龄)。与传统的日历年龄不同，生物学年龄更能反映一个人的真实健康状况和衰老速度。 全新升级甲基化时钟, 包含: 生物年龄检测, 心血管系统年龄, 肝肾年龄，神经系统年龄，免疫系统年龄。