Optic Atrophy, Hereditary, Leber

根据WHO发布的《世界视力报告》数据显示，2020年全球有超40亿患者受到眼科疾病的困扰。受各种因素影响，眼科疾病患者人数正在逐年攀升。虽然患者市场庞大，但因为眼睛结构复杂，许多结构的改变往往具有不可逆性。药物的治疗也许可以缓解一部分症状，却无法改变病变的结构。新兴治疗手段的出现，为眼科疾病患者带来了曙光。以大部分遗传性的眼科疾病为例，这些疾病多与基因突变有关，而基因治疗是目前公认的治疗基因突变等遗传疾病的有效手段。2017年和2018年，FDA和EMA相继批准了第一款眼科基因治疗药物voretigene neparvovec（Luxturna，Spark Therapeutics），用于治疗双拷贝RPE65基因突变导致的遗传性视网膜病疾病，让该类患者实现了真正意义上的重见光明。这无疑点燃了眼科基因治疗赛道的热情。看准这一蓝海，诺华、罗氏、赛诺菲、再生元、艾伯维等大型企业早已在眼科基因治疗领域有所布局，亦有越来越多的新兴企业加入该赛道，法国眼科基因治疗企业SparingVision便是今天的主角。手握资金超9亿，背靠巴黎视觉研究所SparingVision创立于2016年，总部位于法国巴黎，是一家专注于开发致盲遗传性视网膜疾病的基因组药物企业。该公司由巴黎视觉研究所（Paris Vision Institute）分拆而来，成立至今总共完成过三轮融资，融资金额累计1.195亿欧元（约合人民币9.312亿元），投资机构包括4BIO Capital、UPMC Enterprises、Bpifrance、Ysios Capital、Jeito Capital等国际优秀投资机构。SparingVision融资历史，根据公开资料整理不仅投资团队强大，SparingVision的科学创始团队也大有来头。其科学创始人为José Alain Sahel博士和Thierry Léveillard博士，这两位都是巴黎视觉研究所的“骨灰级元老”。Sahel博士是匹兹堡大学医学院眼科系的主席和杰出教授、匹兹堡大学眼科中心主任、眼科耳鼻喉基金会捐赠主席，并于2008年至2020年创立了巴黎视觉研究所并指导了相关工作，他还在2006年至2019年间创立了法国国家视网膜营养不良参考中心并指导了相关工作。基于数十年的科研和产业化经验，Sahel博士开发了干细胞植入、基因治疗、创新药理学方法和视网膜假体等多种眼科疾病疗法，用于治疗视网膜色素变性、其他视网膜营养不良、年龄相关性黄斑变性和其他目前无法治愈的视力损伤等眼科疾病，如Leber遗传性视神经病变。在过去的十几年间，Sahel博士还领导了“光遗传疗法（optogenetic therapy）”这种新型基因技术的开创性工作。与传统基因疗法不同，光遗传疗法可通过将DNA插入神经元，利用光敏通道蛋白（ChR）使神经元响应光照，从而帮助所有光感受器受损患者重建光明。Sahel博士团队通过该疗法，帮助一名失明40年的视网膜色素变性患者恢复了部分视力，相关研究发表在了知名期刊《Nature Medicine》上。此外，Sahel博士还参与发表了700多篇文章，是40多项专利的联合发明人。基于这些成果，他联合创办了Fovea制药公司（后来被赛诺菲收购），还担任了除SparingVision之外，包括GenSight Biologics Inc.、Pixium Vision Inc.、Tinak Healthcare、Chronolife、Prophesee、SharpEye、Vegavet、Avista、Tenpoint等公司的科学联合创始人。SparingVision的另一位科学联合创始人Léveillard博士也在法国国家健康与医学研究院参与创建了视觉研究所，他还是该研究所的主任兼研究员。近年来，Léveillard博士的主要研究方向为遗传性视网膜变性的信号传递和治疗以及神经退行性疾病治疗。基于数年的研究积累，Léveillard博士在2005年创建了Fovea-Pharmaceuticals公司，以利用高含量筛选技术来确定治疗视网膜疾病的新分子。此外，Léveillard博士还是Rod derived Cone Viability Factor（视杆细胞来源视锥细胞活性因子）相关技术的主要发明人。视杆细胞来源视锥细胞活性因子可以在人类视锥细胞的光感受器细胞上与跨膜肽结合，这种结合可以给临近的光感受器细胞带来更多的葡萄糖，从而给光感受器细胞带来更多的养分并且减慢、甚至阻止光感受器凋亡的速度，从而减少视力丢失。此前，SparingVision公司投资了1550万欧元（约合人民币1.2亿元）来完成这项研究。聚焦200万患者，与基因编辑龙头达成合作在团队和资金的共同推动下，SparingVision基于AAV载体递送系统，以及基因编辑技术，开发针对遗传性视网膜疾病（IRD）的眼科基因疗法。体内基因治疗眼科疾病的策略，图源SparingVision官网值得一提的是，在突破基因治疗领域行业痛点时，SparingVision选择站在“巨人的肩上”——通过与基因编辑先驱企业Intellia合作，研究和开发新型自灭活 AAV载体和基于LNP载体的递送技术，以解决 CRISPR/Cas9 基因编辑在视网膜递送方面的问题。Intellia这家企业想必大家都不陌生，其由诺奖得主Doudna联合创办。该公司致力于将基于CRISPR / Cas9技术的研发药物快速转化推向临床，为各种癌症和自身免疫性疾病开发新颖的工程细胞疗法。目前，SparingVision已建立了六条研发管线，其中三条为自研管线，三条为合作管线。其自研管线的适应症均为色素性视网膜炎（RP，视杆细胞营养不良）。RP是IRD最常见的疾病形式，其他 IRD 形式包括视锥/视杆营养不良 (CD/CRD)、莱伯先天性黑蒙（LCA）、黄斑营养不良（MD）、全色盲（视杆细胞单色性）等。在研管线，图源SparingVision官网RP是一种罕见的遗传性疾病，由影响视网膜的 80 多个基因（迄今为止已确定）变异引起。这些基因携带制造视网膜内细胞正常功能所需的蛋白质的指令，称为光感受器。当这些基因发生有害变异时，将影响制造所需的蛋白质的功能，从而限制细胞的功能。患有 RP 的人，随着视网膜感光细胞逐渐死亡，会出现视力丧失。据估计，这种疾病影响了全世界近200万人，大约每3500人中就有1个患者，但目前行业内还没有治疗方法可以治疗这种罕见的视网膜疾病。因此，SparingVision 的三条自研管线一旦获批上市，200万RP将迎来新的基因非依赖性治疗方法，临床市场空间巨大。核心管线临床取得重大进展，全球药企同步发力今年1月，SparingVision宣布其核心管线SPVN06 的Ⅰ/Ⅱ期临床试验（PRODYGY，NCT05748873）取得重大进展。该试验现已进入剂量递增阶段的最终剂量组（第 1 部分），第 2 部分预计将于 2024 年第二季度开始，主要终点将于 2025 年下半年达到。SPVN06旨在阻止或减缓遗传性视网膜疾病（IRD）和干性年龄相关性黄斑变性（AMD）的疾病进展，可通过单一视网膜下注射，递送表达RdCVF与RdCVFL神经营养因子至视网膜色素上皮层，预计能够提供长效的神经保护作用，以避免中重度视网膜色素变性患者的疾病进展。此前，SPVN06在欧洲已被授予孤儿药称号。紧随而后的2月，SparingVision公布了SPVN06的Ⅰ/Ⅱ期PRODYGY临床试验的初步安全性数据。研究数据显示，接受低剂量SPVN06治疗的三名患者，其初步六个月数据显示，无严重不良事件、明显的炎症、停药或剂量限制性毒性。此外，另接受中等剂量治疗的三名患者在一个月内的数据也证实了这些发现。此外，SparingVision在 ASGCT 2023大会上展示了另一条核心管线SPVN20的积极数据。该管线源于2021年4月SparingVision收购生物技术公司GAMUT Therapeutics，主要用于恢复具有休眠视锥细胞的、晚期视网膜色素变性患者的视力和色觉。SPVN20的作用模式是通过引入G蛋白偶联内向整流钾（GIRK）通道，重新激活休眠中的视锥细胞的功能。在 ASGCT 2023会议上，SparingVision首次分享了SPVN20的概念验证数据。SparingVision首席发展科学官Florence Lorget表示，“这些数据对于我们迈向SPVN20的IND至关重要。”除了SparingVision好消息接连不断之外，近年来ProQR Therapeutics、REGENEXBIO、MeiraGTx、Allergan、GenSight Biologics、Spark Therapeutics等海外企业也在眼科基因治疗领域频发喜报。在国内，纽福斯生物、瑞风生物、中因科技、朗信生物、鼎新生物、辉大基因、金唯科、安龙生物、领诺医药、因诺惟康、凌意生物、目镜生物、星眸生物、九天生物等数十家企业也在积极布局眼科基因治疗赛道。目前，已有多种致病基因在眼病中被确认，已经定义的眼科遗传病就有近580种，眼病致病基因近400个。仅在中国，每年就有新增盲人约45万人，低视力人群135万人。未来，随着患者人群的不断增加和适应症的不断扩大，相信全球眼科基因治疗产业链会加速突破基因治疗行业痛点，为数以万计的眼科疾病患者带来更安全、有效的疗法。动脉网第八届未来医疗100强大会现已升级为，将于2024年5月7日-10日在北京·北人亦创国际会展中心盛大举行。本届展会为15000+人次、10000平规模，围绕新产品、新技术、新服务、新生态、新合作构建体系，为医疗健康产业的创新力展示搭建最佳舞台。这里是，公认的医疗产业创新洞察的生成地，年度趋势分享与学习交流的口碑盛会；优秀的医疗创新企业和创新产品都在这，是企业展示创新和面谈合作的最佳场景；这里有，最具前瞻力的思享盛会：500+大咖嘉宾莅临分享，3天主论坛、40余场主题论坛，只做干货议题！最具创新力的生态链接：5大展区，200+首发首创新品、3000+企业、500+投资团，全球买手云集！最具影响力的榜单发布：上市公司创新力榜+未来医疗100强榜+创新力产品榜，700+上榜企业现场交流！目前已有超过600家企业和产品确认参加展会，展览面积预订超过70%，全球买手团已合作了印度尼西亚、新加坡、比利时、爱尔兰、西班牙、德国、澳大利亚、英国、加拿大等国家。余下的合作席位已不多，欢迎企业、品牌方、买手团或相关组织洽谈参会。在这个充满不确定性的时代，寻求高价值资源和高效率链接，将是您的首选。即刻报名，限时福利！声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

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 its financial calendar for 2024. Information Date* 2024 1Q Cash Position April 4, 2024 Annual General Meeting May 29, 2024 2024 2Q Cash Position July 23, 2024 2024 First-Half Financial Update and Statements September 23, 2024 2024 3Q Cash Position October 24, 2024 2024 4Q Cash Position January 23, 2025 * This financial calendar is provided for information only and may be subject to changes. The Company’s updated financial calendar is available on its corporate website. 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, LUMEVOQ® (GS010; lenadogene nolparvovec), is an investigational compound and has not been registered in any country at this stage, developed for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. 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.

Advanced discussions ongoing to secure financing until resumption of early access program (AAC/AAP) expected in Q3 2024 Full alignment sought with regulatory agencies prior to launch of a global Phase III trial supporting both US and EU regulatory submissions for registration of LUMEVOQ® Discussions ongoing on strategic options, including M&A and out-licensing PARIS--(BUSINESS WIRE)-- Regulatory News: GenSight Biologics ("GenSight Biologics" or the "Company") (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 reported its cash position as of March 31, 2024 and provided a business update. “We are currently fully engaged in active discussions to secure funding for our operations until the resumption of our early access program, whose supply is our main immediate-term priority," commented Laurence Rodriguez, CEO of GenSight Biologics. "Simultaneously, we are actively working on refining the design of the RECOVER PIII study, in order to both fulfil regulatory requirements and support marketing authorization in both the United States and Europe.” Cash position as of March 31, 2024 GenSight Biologics’ cash and cash equivalents totalled €2.2 million as of March 31, 2024, compared to €2.1 million as of December 31, 2023. The Company completed a successful offering in February 2024 for a total gross amount of €5 million and has continued to work on cash preservation measures, notably additional savings and obtaining waivers from existing creditors1. The Company does not have sufficient net working capital to meet its obligations over the next 12 months but only until end of April 2024. The Company is currently engaged in active discussions to secure financing for its activities from the end of April 2024 to Q3 2024, when the early access program in France (AAC - autorisation d’accès compassionnel, formerly known as ATU - autorisation temporaire d’utilisation) is expected to resume. Once the AAC/AAP program resumes, the Company estimates that the cash runway would be extended to the end of Q1 2025. The net funding requirement for the next 12 months is estimated at €9 million (including the anticipated income from the resumption of the AAC/AAP program in France in Q3 2024), in view of the Company's need to finance its ongoing activities. In parallel, the Company is also advancing on a number of discussions with potential partners on strategic opportunities, including a possible merger, acquisition or licensing deal, assessed as one of the relevant options to move forward. Business update GenSight successfully manufactured two Drug Substance (DS) batches of LUMEVOQ® meeting Good Manufacturing Practice (GMP) standards in September and November 2023. To optimize vial availability for patients, the decision was made to mix these batches into one Drug Product (DP) batch, slated for release and inclusion in the EAP resumption in Q3 2024. In January 2024, GenSight received constructive feedback from the FDA regarding the design of the Phase III trial RECOVER, which had been previously shared with EMA (European Medicine Agency) and UK’s MHRA (Medicines and Healthcare products Regulatory Agency). The Company is currently refining the RECOVER study design to incorporate feedback from regulatory agencies prior to the launch of the study, in order to both fulfil regulatory requirements and then support both US and EU regulatory submissions for registration. Additional consultations with regulatory agencies may be necessary to finalize the study design. RECOVER will be able to begin recruiting once the design is finalized; the product is released for human use; and approval is obtained from local competent authorities and ethics committees. With the Company prioritizing the allocation of the next available LUMEVOQ® vials to supply of the AAP/AAC program and considering the need of refining the RECOVER study design, the inclusion of the first patient in the trial is expected in H2 2025. The duration of the trial will depend on its final design currently being determined. As previously announced, the existing clinical data package, not necessarily including the upcoming RECOVER trial data, could support a marketing authorization application in the UK. The Company plans further discussions with the MHRA to ensure the quickest path towards a regulatory submission. Starting Q3 2024, the Company expects to provide treatment to patients in France through the AAC program. Number of outstanding shares As of March 31, 2024, GenSight Biologics’ number of outstanding shares was 78,370,724 ordinary shares. Detailed information regarding the Company, including its business, financial information, results, perspectives and related risk factors are contained (i) in the Company’s 2022 Universal Registration Document filed with the AMF on May 10, 2023 under number D.23-0406 (the "2022 URD"), and (ii) the amendment to the 2022 URD filed with the AMF on November 21, 2023 under number D.23-0406-A01 (the "Amendment to the 2022 URD"). These documents, as well as other regulated information and all of the Company's press releases, can be accessed on the Company's website ( ) and/or AMF ( ). Your attention is drawn to the risk factors related to the Company and its activities presented in chapter 3 of its 2022 URD and in chapter 2 of the Amendment to the 2022 URD, in particular the liquidity risk presented in the chapter 2.2.1 of the Amendment to the 2022 URD. 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, LUMEVOQ® (GS010; lenadogene nolparvovec), is an investigational compound and has not been registered in any country at this stage, developed for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. 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. ________________________ 1 View source version on businesswire.com: Contacts GenSight Biologics Chief Financial Officer Ivan Tortet itortet@gensight-biologics.com LifeSci Advisors Investor Relations Guillaume van Renterghem gvanrenterghem@lifesciadvisors.com +41 (0)76 735 01 31 Source: GenSight Biologics S.A. View this news release online at: