MCO-010 achieved its primary and key secondary endpoints with statistical significance and no serious adverse events

MCO-010达到了主要和关键的次要终点，具有统计学意义，没有严重的不良事件

Data from the Phase 2b RESTORE trial demonstrate clinically meaningful vision improvement in legally blind individuals with progressive and permanent neurodegeneration of the retina

2b期RESTORE试验的数据表明，视网膜进行性和永久性神经变性的合法盲人的视力改善具有临床意义

RESTORE is the first randomized, controlled trial of a mutation-agnostic gene therapy for a genetic disease

RESTORE是针对遗传疾病的突变不可知基因疗法的首次随机对照试验

Nanoscope anticipates submitting a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the second half of 2024

Nanoscope预计将于2024年下半年向美国食品和药物管理局（FDA）提交生物制品许可证申请（BLA）

DALLAS, March 26, 2024 /PRNewswire/ -- Nanoscope Therapeutics Inc., a late-stage clinical biotechnology company developing gene therapies for inherited retinal diseases and age-related macular degenerations (AMD), today announced positive top-line results after the completion of the 2-year Phase 2b RESTORE randomized, controlled clinical trial of its lead program, MCO-010, a mutation-agnostic gene therapy for patients with permanent and severe vision loss from advanced retinitis pigmentosa (RP)..

达拉斯，2024年3月26日/PRNewswire/--Nanoscope Therapeutics Inc.，一家开发遗传性视网膜疾病和年龄相关性黄斑变性（AMD）基因疗法的晚期临床生物技术公司，今天宣布，在完成其主导项目MCO-010为期2年的2b期恢复随机对照临床试验后，取得了积极的结果。MCO-010是一种针对晚期视网膜色素变性（RP）永久性和严重视力丧失患者的突变不可知基因疗法。

The trial met its primary endpoint, demonstrating a statistically significant improvement of best-corrected visual acuity (BCVA) at week 52 in both the high-dose (0.337 LogMAR; p=0.021) and low-dose (0.382 LogMAR; p=0.029) treatment groups compared to the sham control group (0.050 LogMAR). The Phase 2b RESTORE trial represents the only randomized controlled trial in retinal degenerative disease to demonstrate improvement beyond the clinically important BCVA > 0.3 LogMAR threshold in a statistically significant manner..

该试验达到了其主要终点，表明高剂量（0.337 LogMAR；p=0.021）和低剂量（0.382 LogMAR；p=0.029）治疗组在第52周的最佳矫正视力（BCVA）有统计学显着改善。假对照组（0.050 LogMAR）。2b期RESTORE试验是视网膜退行性疾病中唯一一项随机对照试验，以统计学显着的方式证明其改善程度超过了临床上重要的BCVA>0.3 LogMAR阈值。

Improvements in visual function persisted or increased following week 52 in the study, demonstrating the durable effect of a single intravitreal injection of MCO-010. BCVA improvement at week 76, a key secondary endpoint, was statistically significant in the high-dose treatment group compared to the control group (0.539 LogMAR; p=0.001).

在研究的第52周后，视觉功能的改善持续或增加，证明了单次玻璃体内注射MCO-010的持久效果。与对照组相比，高剂量治疗组在第76周的BCVA改善（一个关键的次要终点）具有统计学意义（0.539 LogMAR；p=0.001）。

At week 76, the improvement in BCVA in the low-dose treatment group was not statistically significant compared to control (0.374 LogMAR; p=0.065). These results are consistent with what has been previously observed in the earlier Phase 1/2a open-label study. The high-dose MCO-010 (1.2E11gc/eye) is planned to be the commercial dose..

在第76周，与对照组相比，低剂量治疗组的BCVA改善无统计学意义（0.374 LogMAR；p=0.065）。这些结果与先前在早期1/2a期开放标签研究中观察到的结果一致。计划将高剂量MCO-010（1.2E11gc/眼）作为商业剂量。

In another pre-specified secondary endpoint, the composite functional endpoint of novel multi-luminance shape discrimination and y-mobility testing showed an 89% response rate in both the high-dose and low-dose treatment groups at week 52, offering further support of vision improvement following MCO-010 administration.

在另一个预先指定的次要终点中，新型多亮度形状辨别和y迁移率测试的复合功能终点显示，在第52周，高剂量和低剂量治疗组的反应率均为89%，为MCO-010给药后的视力改善提供了进一步的支持。

Additional data from this clinical trial will be presented in a series of scientific meetings in the coming months, beginning with a presentation at the Annual Scientific Meeting of the Association for Research in Vision and Ophthalmology on May 6, 2024, in Seattle, Washington, by Allen Ho, MD, Director of Retina Research and Co-Director of the Retina Service at Wills Eye Hospital..

这项临床试验的其他数据将在未来几个月的一系列科学会议上发表，首先是2024年5月6日在华盛顿州西雅图举行的视觉与眼科研究协会年度科学会议上由威尔斯眼科医院视网膜研究主任兼视网膜服务联合主任Allen Ho医学博士发表演讲。

MCO-010 was generally well tolerated with no treatment-related serious or severe adverse events reported, consistent with prior studies. The most common adverse events were mild or moderate anterior chamber cell and ocular hypertension. No adverse events of special interest related to intraocular inflammation, such as endophthalmitis, retinitis, retinal vasculitis, retinal occlusive vasculitis, or hypotony, were reported in the treatment groups..

与先前的研究一致，MCO-010通常耐受性良好，未报告与治疗相关的严重或严重不良事件。最常见的不良事件是轻度或中度前房细胞和高眼压。在治疗组中没有报告与眼内炎症有关的特别感兴趣的不良事件，例如眼内炎，视网膜炎，视网膜血管炎，视网膜闭塞性血管炎或低眼压。

'We observed significant vision restoration in many patients with severe vision loss, including those who were completely blind,' said David Boyer, MD an investigator in the trial and Adjunct Clinical Professor of Ophthalmology at the University of Southern California Keck School of Medicine. 'Many patients treated with MCO-010 derived a clinically meaningful benefit measurable on the primary visual function test, and this effect was confirmed by a parallel improvement in functional vision assessments.

“我们观察到许多严重视力丧失的患者，包括完全失明的患者，视力明显恢复，”该试验的研究者、南加州大学凯克医学院眼科副临床教授DavidBoyer说许多接受MCO-010治疗的患者在主要视觉功能测试中获得了临床上有意义的益处，并且这种效果通过功能视力评估的平行改善得到了证实。

If approved, MCO-010 is poised to make a positive, meaningful impact on the lives of patients affected by this debilitating condition.'.

如果获得批准，MCO-010有望对受这种衰弱状况影响的患者的生活产生积极而有意义的影响。”

Based on these results, Nanoscope intends to submit a BLA to the U.S. FDA in the second half of 2024 as the first step in executing its global regulatory and commercialization strategy.

基于这些结果，Nanoscope打算在2024年下半年向美国FDA提交BLA，作为执行其全球监管和商业化战略的第一步。

'I am thrilled to see that MCO-010 has the potential to improve vision in patients with advanced RP,' said Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates and Clinical Professor at the University of Nevada, Reno School of Medicine. 'This is a pivotal moment for the field of ocular gene therapy to have a potential intravitreal mutation-agnostic treatment for RP, a disease that has no available treatment currently and leads to permanent vision loss.'.

Sierra Eye Associates临床研究主任兼内华达大学雷诺医学院临床教授、医学博士、硕士、FASRS Arshad M.Khanani说：“我很高兴看到MCO-010有可能改善晚期RP患者的视力。”这是眼部基因治疗领域对RP进行潜在的玻璃体内突变不可知治疗的关键时刻，RP是一种目前尚无可用治疗方法并导致永久性视力丧失的疾病。”

'Nanoscope is at the forefront of advancing optogenetics into a tangible therapeutic solution for patients with RP,' said Sulagna Bhattacharya, co-founder and Chief Executive Officer of Nanoscope. 'The compelling data from the most recent analyses of the RESTORE trial at week 76 provide additional validation of Nanoscope's versatile MCO platform, which is driving our expanding pipeline of programs in both Stargardt disease and geographic atrophy (GA) due to age-related macular degeneration (AMD).

Nanoscope联合创始人兼首席执行官苏拉娜·巴塔查里亚（SulagnaBhattacharya）说，Nanoscope处于将光遗传学推进RP患者有形治疗方案的前沿第76周RESTORE试验的最新分析提供了令人信服的数据，进一步验证了Nanoscope的多功能MCO平台，该平台正在推动我们扩大Stargardt病和年龄相关性黄斑变性（AMD）引起的地理萎缩（GA）的程序管道。

We extend our heartfelt appreciation to the trial participants and their families, as well as to the investigators and all those who contributed to this groundbreaking trial and its successful completion.'.

我们衷心感谢试验参与者及其家人，以及调查人员和所有为这项开创性试验及其成功完成做出贡献的人。”

These results represent the first evidence of effectiveness of a mutation-agnostic gene therapy for a genetic disease. These results reflect more than a decade of innovation across all aspects of the MCO-010 program, including vector design, manufacturing, and clinical trial design, as well as the development of novel functional vision endpoints for this population with severe vision loss..

这些结果代表了突变不可知基因疗法对遗传疾病有效性的第一个证据。这些结果反映了MCO-010计划各个方面十多年的创新，包括载体设计，制造和临床试验设计，以及为严重视力丧失人群开发新型功能性视力终点。

'These results are the culmination of more than a decade of work by numerous dedicated individuals, underscoring the potential of our unique broadband, highly photosensitive, and rapid MCO-010 platform,' said Samarendra Mohanty, PhD, co-founder, President, and Chief Scientific Officer of Nanoscope. 'This achievement marks a significant milestone in the field of mutation-agnostic gene therapy, firmly establishing the promise of optogenetics as a therapeutic modality.

Nanoscope联合创始人、总裁兼首席科学官萨马兰德拉·莫汉蒂（Samarendra Mohanty）博士说：“这些结果是众多敬业人士十多年工作的结晶，突显了我们独特的宽带、高度光敏和快速MCO-010平台的潜力。”这一成就标志着突变不可知基因治疗领域的一个重要里程碑，坚定地确立了光遗传学作为一种治疗方式的前景。

We extend our sincere gratitude to the National Eye Institute-NIH and collaborators for their invaluable contributions in realizing the therapeutic potential of MCO therapy, offering hope for vision restoration to patients regardless of their underlying genetic mutation.'.

我们衷心感谢美国国立卫生研究院国家眼科研究所及其合作者在实现MCO治疗的治疗潜力方面做出的宝贵贡献，为患者提供了视力恢复的希望，无论其潜在的基因突变如何。”

The multicenter, Phase 2b trial randomized 28 subjects with severe vision loss and confirmed clinical diagnosis of RP. One randomized subject, who withdrew consent before baseline measurements and study intervention, was not included in the mITT population. Reported results are from the mITT population that included all randomized subjects who received the intervention in the study eye (MCO-010 or control): 18 subjects in the MCO-010 groups and 9 subjects in the control group.

这项多中心2b期临床试验将28名患有严重视力丧失并确诊为RP的受试者随机分组。一名在基线测量和研究干预之前撤回同意的随机受试者不包括在mITT人群中。报告的结果来自mITT人群，其中包括在研究眼中接受干预的所有随机受试者（MCO-010或对照）：MCO-010组中的18名受试者和对照组中的9名受试者。

For the primary and key secondary endpoints, subjects were evaluated at multiple time points over two years to assess BCVA, measured by the Freiburg visual acuity test..

对于主要和关键的次要终点，受试者在两年内的多个时间点进行评估，以评估通过弗莱堡视力测试测量的BCVA。

A linear mixed-effects model for repeated measures (MMRM) was performed on the primary and key secondary endpoints, where the visual acuity data from all post-baseline visits was included in the model, with baseline visual acuity as a covariate.

在主要和关键次要终点上进行了重复测量的线性混合效应模型（MMRM），其中所有基线后访视的视力数据都包含在模型中，基线视力作为协变量。

Comparisons between the treatment groups were performed using a Hochberg procedure to adjust for multiple comparisons against the control. Using the results obtained from the MMRM model, the p-values from the two comparisons of the MCO-010 groups versus the control were ordered from largest to smallest..

使用Hochberg程序进行治疗组之间的比较，以调整与对照的多重比较。使用从MMRM模型获得的结果，MCO-010组与对照组的两次比较的p值从最大到最小排序。

Primary and key secondary visual acuity endpoint results being reported are based on regulatory discussions, as previously announced on January 18, 2024, and align the study endpoints with the originally intended study objectives. A revised statistical analysis plan (SAP) was finalized and submitted to regulators before the completion of week 76 and later time points of the study..

报告的主要和关键次要视力终点结果基于监管讨论，如先前于2024年1月18日宣布的那样，并将研究终点与最初预期的研究目标相一致。修订后的统计分析计划（SAP）已最终确定，并在第76周及以后的研究时间点完成之前提交给监管机构。

The functional vision was assessed by evaluating subject performance in object recognition or navigating a mobility course under a variety of light levels encountered in activities of daily living.

通过评估受试者在物体识别中的表现或在日常生活活动中遇到的各种光照水平下导航移动课程来评估功能性视力。

About Retinitis Pigmentosa

关于色素性视网膜炎

Retinitis Pigmentosa (RP) encompasses a group of rare genetic disorders in which the retina's photoreceptor cells degrade over time, leading to impaired vision and eventual blindness. These disorders are believed to be linked to over 100 different gene mutations. Approximately 100,000 people in the U.S.

色素性视网膜炎（RP）包括一组罕见的遗传性疾病，其中视网膜的感光细胞随着时间的推移而降解，导致视力受损和最终失明。据信这些疾病与100多种不同的基因突变有关。美国大约有100000人。

and an estimated 2 million people worldwide suffer from RP, making it the leading cause of inheritable blindness..

据估计，全世界有200万人患有RP，使其成为遗传性失明的主要原因。

About MCO-010

关于MCO-010

Current gene therapies aim to treat patients with specific genetic mutations and are further limited in advanced diseases with degenerated outer retina cells. Ambient-light activatable MCO optogenetic monotherapy targets abundant inner retinal neurons and has the potential to restore vision permanently lost due to advanced RP.

目前的基因疗法旨在治疗具有特定基因突变的患者，并且在视网膜外细胞退化的晚期疾病中受到进一步限制。环境光可激活的MCO光遗传学单一疗法靶向丰富的内部视网膜神经元，并有可能恢复由于晚期RP而永久丧失的视力。

MCO-010 (sonpiretigene isteparvovec, suspension for intravitreal injection) is the only broadband, fast, and highly light-sensitive opsin currently in clinical trials. With bipolar cell targeting via mGluR6 promoter-enhancer, the MCO-010 expression cassette is designed for restoring high-quality vision in real-world environments.

MCO-010（sonpiretigene isteparvovec，玻璃体内注射用悬浮液）是目前临床试验中唯一的宽带，快速且高度光敏的视蛋白。通过mGluR6启动子增强子靶向双极细胞，MCO-010表达盒旨在恢复现实环境中的高质量视力。

The proprietary AAV2 vector allows robust transduction of MCO-010 in bipolar cells upon intravitreal injection. The Phase 1/2a study of MCO-010 in advanced RP patients demonstrated favorable safety and dose-dependent improvement in visual acuity..

专有的AAV2载体允许在玻璃体内注射后在双极细胞中强烈转导MCO-010。MCO-010在晚期RP患者中的1/2a期研究表明，视力有良好的安全性和剂量依赖性改善。

About Nanoscope Therapeutics Inc.

关于Nanoscope Therapeutics Inc

Nanoscope Therapeutics is developing gene-agnostic, sight-restoring optogenetic therapies for the millions of patients blinded by inherited retinal diseases, for which no cure exists. The company's lead asset, MCO-010, recently completed the RESTORE Phase 2b multicenter, randomized, double-masked, sham-controlled clinical trial in the U.S.

Nanoscope Therapeutics正在为数百万遗传性视网膜疾病致盲的患者开发基因不可知的视力恢复光遗传学疗法，目前尚无治愈方法。该公司的主要资产MCO-010最近在美国完成了RESTORE 2b期多中心，随机，双盲，假对照临床试验。

for retinitis pigmentosa (NCT04945772). The company has also recently completed the Phase 2 STARLIGHT trial of MCO-010 therapy in patients with Stargardt disease (NCT05417126 ). MCO-010 has received FDA fast-track designations and FDA orphan drug designations for both RP and Stargardt disease. Preclinical assets include non-viral laser-delivered MCO-020 gene therapy for GA due to AMD..

用于色素性视网膜炎（NCT04945772）。该公司最近还完成了Stargardt病患者MCO-010治疗的2期STARLIGHT试验（NCT05417126）。MCO-010已获得FDA针对RP和Stargardt病的快速通道指定和FDA孤儿药指定。临床前资产包括非病毒性激光递送的MCO-020基因治疗AMD引起的GA。