Bionic Sight LLC

从猕猴实验，到2024年7月Neuralink即将迎来第二例人体试验，我们正在频频经历脑机接口所创造的历史时刻。 此前的2024年4月，Elon Musk还在社交平台上分享了Neuralink的另一个好消息——“The Blindsight implant is already working in monkeys”。我们可以就此推断，以Neuralink为代表的侵入式脑机接口企业将有望实现“盲人复明”。 除了Elon Musk以外，还有一家脑机接口企业同样致力于使“盲人复明”。这就是由Neuralink的联合创始人兼前总裁Max Hodak所创办的Science Corporation。 Science CEO Max Hodak（左一） 图源：华盛顿邮报    师从脑机接口之父， 一位成功的跨领域连续创业者 Science CEO Max Hodak和一众脑机接口赛道的明星创业者一样，拥有亮眼的履历背景。 除了在Neuralink担任总裁的创业经历外，毕业于杜克大学的Max Hodak还曾在大学二年级的时候创办MyFit并获得100万美元的投资，这家企业后被纳维斯（Naviance）收购。随后的两年内，Max Hodak选择继续完成他在生物医学工程专业的学业，师从被誉为“脑机接口之父”的杜克大学神经生物学、神经学和生物医学工程教授Miguel Nicolelis。 2012年毕业后，Max Hodak选择再次创业，只不过这次依旧和脑机接口无缘。Max Hodak第二次创业所成立的Transcriptic是一款基于云服务的生命科学研究平台。这个项目获得包括Google Ventures、Data Collective、Silicon Valley Bank等明星投资机构的青睐，累计融资超过3000万美元。 在科技行业兜兜转转5年后，Max Hodak重新回到了起点。大学期间Max Hodak曾在杜克大学Miguel Nicolelis教授的实验室担任助理研究员，参与了恒河猴的脑机接口的研究。此次创业便是与其他7位合伙人一起成立的Neuralink，专注侵入式脑机接口的开发。 2021年4月9日，Neuralink宣布在猴子的大脑中植入了脑机接口，控制猴子玩电子游戏。随后的5月2日Max Hodak正式宣布离职，并在分道扬镳之后，创办了一家全新的脑机接口公司科学公司Science。截至目前，Science已累计融资1.6亿美元。 Science开发的第一个产品是名为“Science Eye”的视觉假体（Visual Prostheses），目前主要针对原发性视网膜色素变性（RP）、老年性黄斑变性（AMD）与少年性黄斑变性（Stargardt）等因感光细胞死亡所造成的严重失明疾病。 具体而言，Science Eye是一种组合设备，包含两个部分。首先是植入物，由一个无线电源线圈和直接插入视网膜的超薄柔性micro-LED组成。第二个是一副无框眼镜，其大小和形状与常规眼镜相似，内含微型红外摄像头和感应电源线圈。 但在设备之前，Science还借助了一种新型基因疗法工具——光遗传学基因疗法（Optogenetic Therapy）。该疗法可通过将视蛋白（Opsins）注射到感光细胞，利用光敏通道蛋白（ChR）使神经元响应光照，增强眼球后部视网膜组织对光的敏感性，从而帮助视细胞受损的患者重见光明。   基因疗法+植入式视觉接口， 重塑视觉使“盲人复明” 从“看”这个动作的背后原理来看，光线通过晶状体进入眼睛，在视网膜上形成图像。视网膜上的感光细胞（视杆细胞和视锥细胞）接收到光线刺激后，会产生神经冲动。这些神经冲动通过视神经纤维传递给大脑皮层，最终形成视觉感知。 在视网膜的色素变性中，感光细胞中的视杆细胞和视锥细胞被分解后死亡，这造成周边视觉的丧失，并发展成管状视野，患者必须转动整个头部才能看到周围的世界。不久后，彻底失明就会随之而来。 值得庆幸的是，在这个发病过程中感光细胞的分解并没有减弱大脑处理电信号的能力，而且更关键的是，视网膜中的第三级神经元——神经节细胞（RGCs）也依然完好无损。因此，Science Eye要做的第一步就是绕开视觉发生路径，将视蛋白直接传输到神经节细胞，使其对特定波长的光敏感，成为新的“感光细胞”。 第一步：靶向神经节细胞 图源：华盛顿邮报 第二步则是向患者视网膜安装植入物——超薄柔性micro-LED。通过手术将设备尾端的光片（Lightsheet）放置到新的“感光细胞”上，并利用micro LED发出的特定波长的光驱动这些感光细胞，使其向大脑皮层发出电信号。  第二步：超薄柔性micro-LED 图源：华盛顿邮报 具体而言，这款植入物名为“FlexLED”，是一种厚度只有30μm的超薄柔性无线Micro LED，包含了8192个像素，像素发光面积为66μm²。通过手术，医生将FlexLED固定在眼球的背面使用，随附的电子组件则安装在眼睛的顶部。据Max Hodak在公开采访中透露，这项视觉假体技术的分辨率可达到iPhone屏幕的8倍。 超薄柔性无线Micro LED与随附的电子组件 图源：science官网 第三步是一款名为“PRIMA”的特殊眼镜。这款眼镜上配有微型红外摄像头和感应电源线圈，可以将图像信号投射到Micro LED上，激活经过改造的感光细胞，从而将信息带回信号链，最终在大脑中产生视觉。 第三步：PRIMA眼镜 图源：华盛顿邮报 依托这三步，即便是天生眼盲的人，也有可能重见光明。Science目前已在兔子测试模型中成功将RGCs转化为感光细胞，并“照亮”大脑。针对最令人关注的临床试验问题，Max Hodak也在接受华盛顿邮报的采访时表示，Science Eye的人体临床试验将在2025年之前开展。   收购眼科器械上市公司， 6500万美元扩建工厂 视觉假体这个概念本身并不足够“新颖”，除了Science，全球也有许多创新企业在研发视觉假体，例如Second Sight、Pixium Vision SA。但Max Hodak在研究过市面上现有技术后表示：“早期的行业领导者使用的是传统电极，但从长远来看，这些电极无法达到真正意义上的高分辨率视觉。” 同时，全球范围内也有一些企业在开发光遗传学技术，例如Bionic Sight、GenSight等。“这些公司使用安装在眼镜上的激光投影仪来驱动视蛋白，这种蛋白质不会随着眼睛移动，而Science Eye采用的灵活的微型柔性Micro LED技术，可以在患者环顾四周和移动时，保持感光细胞到大脑皮层图像的持续映射。”Max Hodak称。 值得一提的是，2024年4月Science完成对Pixium Vision SA的知识产权和相关资产收购，这也是Science Eye第三步PRIMA技术的来源。Pixium Vision在2023年年底关键试验得出最终结果之前，就几乎耗尽了所有现金，被Science收购时，公司正值倒闭的边缘，但这不是因为技术的失败而是由于一次关键合并交易的取消。 PRIMA于2023年获得美国FDA突破性医疗器械认定，目前正在进行三项人体临床试验，尽管Pixium Vision和Science都未对外发布完整的试验数据集，但Max Hodak和IEEE Spectrum videos曾公开分享了三个AMD患者使用Prima的视频。视频显示：这三个患者在Prima帮助下，可以缓慢但流利地阅读精装书、填填字游戏和打牌。 对于本次收购，Max Hodak称：“Elon想做什么就做什么，但我们需要一些能够推动未来真正发展的东西。就对患者和社会的价值而言，Prima拥有足够大的能力和潜力帮助我们实现抱负。” Max Hodak也曾将Science的技术与现有技术路径做对比，相较于植入脑部的N1芯片，他认为“只要视神经完好无损，视网膜就是恢复大脑视力的理想场所，因为大脑视觉皮层太复杂、分散，手术植入难度也更大。但从光遗传学和Prima两个技术路径来看，我们尚不知道哪个能最终帮助视觉障碍的人恢复视力，但我认为光遗传学将比Prima的电刺激更强大。” 技术落地方面，2023年初Science收购了一家美国MEMS代工厂，打造了“Science Foundry”。2024年7月，Science宣布决定再投资6500万美元，扩建超5000平方米的制造工厂，以支持Science Eye和PRIMA等尖端技术产品的制造生产。 同时，Science Foundry还将利用公司先进的MEMS制造能力为客户提供定制化的开发服务，主要包括薄膜柔性电极技术（Thin Film Electrode Standard Technology）、多晶硅标准技术（Polysilicon Standard Technology）、压电标准技术（Piezo Standard Technology）和绝缘衬底上的硅标准技术（Silicon-on-Insulator Standard Technology）。这四大平台将帮助用户将开发时间从数月缩短到数周内，减少前期的工艺开发投资，推动脑机接口产业的快速发展和落地。 如果您想对接文章中提到的项目，或您的项目想被动脉网报道，或者发布融资新闻，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。 近 期 推 荐 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

Applied Genetic Technologies Corporation (Nasdaq: AGTC), a clinical stage biotechnology company focused on the development and commercialization of adeno-associated virus (AAV)-based gene therapies for the treatment of rare and debilitating diseases with an initial focus on inherited retinal diseases, today reported updated interim three-month pediatric results and additional adult safety results out to as long as 24 months from its ongoing Phase 1/2 dose escalation study of AGTC-401. AGTC-401 is a recombinant AAV viral vector-based gene therapy targeting mutations in the CNGB3 gene in patients with achromatopsia (ACHMB3). Data from seven pediatric patients support previously reported findings from adults treated with AGTC-401, which demonstrated encouraging biologic activity and a favorable safety profile. There were no new Suspected Unexpected Serious Adverse Reactions (SUSARs) and for the three previously reported SUSARs, the inflammation continues to improve with steroid treatment. Based on the totality of the ACHMB3 data generated to date from 31 patients over as long as 24 months, AGTC plans to advance the clinical development of AGTC-401 subject to consultation with the U.S. Food and Drug Administration (FDA) at an End-of-Phase 2 (EOP2) meeting in the first half of 2022. The Company also reported updated results from a parallel study of AGTC-402 targeting CNGA3 mutations in patients with achromatopsia that are consistent with previously reported results in adults, provide no indication of clinical improvements, and do not support further clinical development. Most patients with CNGA3 mutations express a mutant protein that is not typically found in patients with CNGB3 mutations, which the Company believes may have impacted results seen in patients that received AGTC-402. AGTC will continue to follow the ACHMA3 patients for long-term safety observations. “The three-month pediatric findings provide further evidence for the strong potential of our product candidate for patients with ACHMB3, and we look forward to continuing our discussions with the regulatory agencies to determine the best path forward to bring this important therapy to patients,” said Sue Washer, President and Chief Executive Officer of AGTC. “We understand the challenges that patients with achromatopsia face in their daily lives and our team remains dedicated to advancing this program toward commercialization. These additional data provide us the opportunity to help inform the next phase of clinical development and we thank the patients and investigators for their participation in this important clinical trial.” In the Phase 1/2 dose escalation study of AGTC-401 in ACHMB3 patients, a total of 21 adults were treated over a 100-fold dose range in five groups and a total of ten pediatric patients were treated at the three highest dose groups. The primary purpose of any Phase1/2 clinical trial is to identify a well-tolerated dose that provides clinical benefit to patients. The Company believes that the data to date support that the 1.1E+12vg/mL dose is well tolerated and provides clinical benefit in both adult and pediatric patients. “We’re pleased to have identified a generally safe and well tolerated dose of AGTC-401 for both adults and pediatric patients when inflammation is controlled,” said Dr. Robert Sisk, MD, Director of Pediatric Vitreoretinal Surgery and Director of Ophthalmic Genetics – Cincinnati Children’s Hospital and the Cincinnati Eye Institute and an investigator in the ongoing AGTC achromatopsia Phase 1/2 trials. “Based on the available pediatric data at three months, which are consistent with previously reported results in adults with ACHMB3, we are encouraged by the biologic activity observed in patients treated with AGTC-401. The achromatopsia community currently faces a significant unmet need and the totality of this data reinforces the promise of AGTC-401 as a potential treatment option if confirmed in future studies.” As previously reported, in both the ACHMB3 and ACHMA3 trials, treatment with the highest doses of AGTC-401 and AGTC-402, respectively, led to three cases of severe ocular inflammation in pediatric patients, which were reported as SUSARs. No new additional SUSARs have been reported and the inflammation in all previously reported SUSARs improved with an adjusted steroid regimen. Two SUSARs (one in ACHMA3 and one in ACHMB3) have since fully resolved and one (ACHMA3) continues to resolve, with all three patients’ best corrected visual acuity returning to baseline. Secondary outcome measures evaluating efficacy were assessed by standard visual function tests such as perimetry. We defined two pediatric patients (17 and 7 years old) in the 1.1E+12 vg/mL dose group as responders based on improvements in visual sensitivity. Therefore, of the three adults and four children (total n=7) in the 1.1E+12 vg/mL dose group, four (>50%) are visual sensitivity responders. These patients also had improvements in quality of life as measured by a patient reported outcome survey developed specifically for patients with achromatopsia. The two other pediatric patients in the 1.1E+12 vg/mL dose group and three pediatric patients ages 7 years and younger in the 3E+12vg/mL dose group (total n=5) could not sufficiently concentrate and consistently complete the visual sensitivity testing. Similar to other trials where endpoints are adapted for young children, AGTC plans to work closely with clinicians and regulators to develop potential adaptations for younger patients for visual sensitivity testing. The Company is currently working on an EOP2 meeting package for the FDA and expects to receive feedback in the first half of 2022. Subject to these discussions with FDA, the Company plans to initiate the next phase of AGTC-401 clinical development. The clinical program will be based on the favorable risk benefit pro the 1.1E+12 vg/mL dose, which had a generally safe and well tolerated safety pro all patients and signs of biologic response based on improvements in visual sensitivity and other measures of visual function. Final data and analysis of both ACHMA3 and ACHMB3 studies will be presented at relevant conferences and published for the ophthalmology community. About Achromatopsia (ACHM) Achromatopsia (ACHM) is an inherited condition caused by mutations in one of several genes, with the two most common being mutations in either the CNGB3 or CNGA3 genes. ACHM is associated with extremely poor visual acuity (most affected individuals are legally blind), extreme light sensitivity resulting in daytime blindness, and complete loss of color discrimination. AGTC is currently developing two separate AAV gene therapy product candidates for the two most prevalent forms of ACHM, caused by either a genetic mutation in the CNGB3 or CNGA3 genes. Together, these two genetic mutations account for up to 75% of the ACHM patient population. About AGTC AGTC is a clinical-stage biotechnology company developing genetic therapies for people with rare and debilitating ophthalmic, otologic and central nervous system (CNS) diseases. AGTC is a leader in designing and constructing all critical gene therapy elements and bringing them together to develop customized therapies with the potential to address unmet patient needs. AGTC’s most advanced clinical programs leverage its best-in-class technology platform to potentially improve vision for patients with inherited retinal diseases. AGTC has active clinical trials in X-linked retinitis pigmentosa (XLRP) and achromatopsia (ACHM CNGB3 and ACHM CNGA3). Its preclinical programs build on the company’s industry leading AAV manufacturing technology and scientific expertise. AGTC is advancing multiple important pipeline candidates to address substantial unmet clinical needs in optogenetics, otology and CNS disorders, and has entered strategic collaborations with companies including Otonomy, Inc., a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology, and Bionic Sight, LLC, an innovator in the emerging field of optogenetics and retinal coding.

GAINESVILLE, Fla. and CAMBRIDGE, Mass., Sept. 07, 2021 (GLOBE NEWSWIRE) --Applied Genetic Technologies Corporation (Nasdaq: AGTC), a biotechnology company conducting human clinical trials of adeno-associated virus (AAV)-based gene therapies for the treatment of rare diseases, today announced that management will be participating in a company presentation at the H.C. Wainwright 23rd Annual Global Investment Conference on September 13th, 2021. Audio webcasts of the presentation can be accessed by visiting A replay will be available on the Company's website following the events. About AGTC AGTC is a clinical-stage biotechnology company developing genetic therapies for people with rare and debilitating ophthalmic, otologic and central nervous system (CNS) diseases. AGTC is a leader in designing and constructing all critical gene therapy elements and bringing them together to develop customized therapies that address real patient needs. AGTC’s most advanced clinical programs leverage its best-in-class technology platform to potentially improve vision for patients with an inherited retinal disease. AGTC has active clinical trials in X-linked retinitis pigmentosa (XLRP) and achromatopsia (ACHM B3 and ACHM A3). Its preclinical programs build on the Company’s industry leading AAV manufacturing technology and scientific expertise. AGTC is advancing multiple important pipeline candidates to address substantial unmet clinical need in optogenetics, otology and CNS disorders. In recent years AGTC has entered into strategic partnerships with companies including Otonomy, Inc., a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology, and Bionic Sight, LLC, an innovator in the emerging field of optogenetics and retinal coding. IR CONTACT: Jonathan Nugent Stern IR T: 212-698-8698 Jonathan.nugent@sternir.com Corporate Contacts: Stephen Potter Chief Business Officer Applied Genetic Technologies Corporation T: (617) 413-2754 spotter@agtc.com