A Phase 1, Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of HG202 High-fidelity CRISPR-Cas13 (hfCas13Y) RNA-targeting Therapy for Neovascular Age-related Macular Degeneration (nAMD)

Age-related macular degeneration (AMD) leads to severe and irreversible vision loss, while neovascular AMD (nAMD) accounts for 80-90% of AMD blindness. Current anti-VEGF therapies are the standard of care, but these therapies require life-long repeated intraocular injections. These frequent intravitreal injections increase the risk of complications, including submacular hemorrhage, intraocular hypertension, inflammation, and retinal detachment. Therefore, repeated treatments for nAMD place a substantial burden on healthcare systems, patients, and their caregivers. Additionally, approximately 25-35% of individuals with aggressive nAMD show suboptimal responses to the anti-VEGF therapies, experience treatment-extended failure, or require intensive, frequent intraocular injections, and do not prevent irreversible vision loss.
HG202 is a CRISPR/Cas13 RNA-editing therapy delivered through one single AAV vector to partially knock down the expression of VEGFA and thus inhibit CNV formation in AMD. The long-term, stable delivery of HG202 following a one-time gene-editing therapy treatment for nAMD may potentially reduce the frequent injections and the potential risks of currently available anti-VEGF therapies since it does not rely on the long-term expression of anti-VEGF antibodies.

开始日期2025-04-01

申办/合作机构

辉大（上海）生物科技有限公司初创企业

NCT06031727 / Recruiting早期临床1期

A Trial to Evaluate the Safety, Tolerability, and Efficacy of CRISPR-Cas13 RNA-editing Therapy Targeting Knockdown of Vascular Endothelial Growth Factor A (HG202) in the Treatment of Neovascular Age-related Macular Degeneration (nAMD)

Age-related macular degeneration (AMD) is a progressive disease leading to severe and irreversible vision loss of which the neovascular AMD (nAMD) accounted for 90% blindness in AMD. nAMD is primarily driven by the perturbation of vascular endothelial growth factor (VEGF). VEGF overexpression leads to abnormal growth of choroidal neovascularization (CNV), which is a hallmark of AMD. Although anti-VEGF agents are effective in treating nAMD, long-term efficacy decreases over time due to the need for repeated injections impacting patient compliance with treatment regimen while patients still may lose vision during the 7th or 8th year of treatment. These frequent intravitreal injections can increase the risk of complications, including submacular hemorrhage, intraocular hypertension, inflammation, and retinal detachment. Furthermore, there are up to 46% of nAMD patients using anti-VEGF agents who have shown poor response or have developed tachyphylaxis with anti-VEGF therapies. HG202 is a CRISPR/Cas13 RNA-editing therapy packaging novel high-fidelity Cas13 technology using one single AAV vector to partially knock-down the expression of VEGFA and thus inhibit CNV formation in AMD patients who are either responsive or non-responsive to anti-VEGF agents. The long-term, stable delivery of HG202 following a one (1) time gene-editing therapy treatment for nAMD could potentially reduce the frequent injection treatment burden of currently available therapies AND treat nAMD patients who are non-responsive to anti-VEGF therapies and have no treatment.

开始日期2023-09-04

申办/合作机构

辉大（上海）生物科技有限公司初创企业

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100 项与 HG-202 相关的临床结果

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100 项与 HG-202 相关的转化医学

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100 项与 HG-202 相关的专利（医药）

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项与 HG-202 相关的新闻（医药）

16 小时之前

·mobihealthnews

FDA clears application for CRISPR RNA-editing therapy developed using AI

Global clinical-stage biotech company HuidaGene Therapeutics has received FDA clearance to move forward with its application for its investigational drug, a CRISPR/Cas13 RNA-editing therapy to treat neovascular age-related macular degeneration (nAMD), dubbed HG202, developed using machine learning and AI. The company used its HG-PRECISE platform (HuidaGene – Platform for Rational Engineering of CRISPR-Cas Identification by Synergic Expertise) to devise the therapy. HG-PRECISE allows for the quick discovery of Cas proteins using AI and machine learning in DNA sequencing. It also provides assembly predictions from a metagenomic database. The company will move forward with a phase one study to evaluate HG202's effectiveness at different doses in patients with nAMD. The company says the BRIGHT trial will begin enrolling patients soon. "Our AI/ML-driven HG-PRECISE platform led us to discover the Cas13X/Y system," Hui Yang, cofounder and chief scientific advisor of HuidaGene, said in a statement. "Building on this basis, my team engineered high-fidelity Cas13Y with efficient editing and low off-target effects, laying out the technical foundation for future clinical applications." THE LARGER TREND Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology, developed more than a decade ago, allows scientists to modify DNA sequences of living organisms. Potential applications range from treatments for genetic disorders to researching disease mechanisms. Gene editing technologies, such as SHERLOCK and DETECTR, are transforming digital diagnostics, enabling rapid detection of infectious diseases like COVID-19. Still, ethical, legal and scientific factors warrant consideration, and instabilities can happen that can be fatal for someone, according to experts. Gene editing can cause irreversible changes, and changes to a DNA sequence can last for generations. Another company working with CRISPR technology is AI-enabled protein design company Profluent, which has leveraged AI to design an open-source gene editor called OpenCRISPR-1, demonstrating the technology can be used to create molecules with the power to edit human DNA.

siRNA基因疗法临床1期临床申请

23 小时之前

·PRNewswire

HuidaGene Therapeutics Receives the First-Ever FDA Clearance of CRISPR/Cas13 RNA-Editing HG202 for Macular Degeneration

HG202 is the first CRISPR/Cas13Y RNA-targeting therapy to enter clinical development and the only clinical-stage CRISPR RNA-editing therapy for age-related macular degeneration Preclinical studies in laser-induced CNV mice showed HG202 reduced CNV area by 87%, outperforming both anti-VEGF antibodies and AAV-anti-VEGF gene therapy SHANGHAI and CLINTON, N.J., Nov. 4, 2024 /PRNewswire/ -- HuidaGene Therapeutics ("HuidaGene"), a global clinical-stage biotechnology company, announced that the U.S. FDA has cleared its investigational new drug (IND) application for HG202, the world's first-ever CRISPR/Cas13 RNA-editing therapy for clinical use in treating neovascular age-related macular degeneration (nAMD), which affects millions worldwide. "This open IND for HG202 by the U.S. FDA-the first regulator to clear CRISPR/Cas13 for clinical development–marks a significant milestone for HuidaGene and the CRISPR RNA-editing field," noted Alvin Luk, Ph.D., M.B.A., C.C.R.A., Co-founder and CEO of HuidaGene. "The strong preclinical data for HG202, combined with promising results from the first-in-human ' SIGHT-I' trial in China, underscored its potential to address AMD using a non-receptor binding pathway through the Cas13 RNA editor to knockdown VEGF-A mRNA." Xin Zhang, M.D., MSc., COO and CMO of HuidaGene, highlighted the urgency of new nAMD treatments: "Up to 46% of AMD patients respond poorly or develop resistance to anti-VEGF therapies. AMD patients deserve safe, effective treatment options. The BRIGHT trial will evaluate HG202's safety and efficacy to address this gap. We look forward to enrolling patients soon." "Our AI/ML-driven HG-PRECISE® platform led us to discover the Cas13X/Y system (Nature Methods 2021)," added Hui Yang, Ph.D., Co-Founder and Chief Scientific Advisor of HuidaGene. "Building on this basis, my team engineered high-fidelity Cas13Y with efficient editing and low off-target effects (Nature Biotechnology 2022), laying out the technical foundation for future clinical applications." BRIGHT Trial of HG202 (NCT06623279) The BRIGHT (an open-la Bel, dose-escalation study for CRISPR/Cas13- RNA target In G t Herapy for the Treatment of neovascular AMD) trial, a Phase 1, dose-finding study, will investigate the safety and efficacy of HG202 at different doses in nAMD patients. Primary endpoints include the safety and tolerability of HG202, with secondary endpoints assessing improvements in visual acuity, retinal thickness, and the need for anti-VEGF injections. About HuidaGene HuidaGene utilizes its proprietary CRISPR-based HG-PRECISE® platform to develop potentially curative genome medicines. The Company is advancing clinical programs, including trials of HG004 (granted ODD & RPDD by FDA) ' LIGHT' trial (NCT06088992) and Phase 1/2 international, master-protocol ' STAR' clinical trial (NCT05906953) for RPE65-associated retinal disease, HG202 RNA-editing therapy ' SIGHT-I' first-in-human trial (NCT06031727) and ' BRIGHT' Phase 1 clinical trial (NCT06623279) for nAMD, HG204 RNA-editing therapy (granted ODD & RPDD by FDA and ODD by EMA) ' HERO' trial (NCT06615206) for MECP2 duplication syndrome, and HG302 DNA-editing therapy (granted ODD & RPDD by FDA) first-in-human ' MUSCLE' trial (NCT06594094) for DMD. The preclinical programs include HG303 DNA-editing for ALS and CRISPR RNA-editing therapy for Alzheimer's. With an extensive intellectual property portfolio, HuidaGene is a leader in genome medicines for neurology and ophthalmology. Learn more at huidagene.com or on LinkedIn. SOURCE HuidaGene Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床申请临床1期siRNA

2024-11-04

·Insight数据库

辉大基因 RNA 编辑疗法获 FDA 批准临床，用于治疗黄斑变性

11 月 4 日，辉大基因宣布，HG202 临床试验申请（IND）已获 FDA 批准，用于新生血管性年龄相关性黄斑变性（nAMD）。截图来源：辉大基因官微 HG202 是辉大基因自主研发的首个高保真 CRISPR/Cas13 RNA 编辑治疗技术临床项目，将 CRISPR/Cas13 RNA 编辑器搭载于单个腺相关病毒（AAV）递送到视网膜，特异性地敲低 VEGF-A mRNA 表达水平，以治疗已接受过现有抗 VEGF 疗法有效或耐药的 nAMD 患者。 2023 年 9 月 6 日，HG202 已在国内完成首例 nAMD 患者给药。在 2024 年 ASGCT 大会上，辉大基因公布了 HG202 用于湿性年龄相关性黄斑变性的初步临床结果（NCT06031727）。截至 2024 年 1 月，5 名受试者签署了 ICF，3 名受试者被纳入低剂量组。受试者 #202 是一名对抗 VEGF 疗法无反应且有抗性的患者，在 8 个月内曾注射过 6 次抗 VEGF 注射，注射前黄斑积液持续存在。受试者 #202 基线包括 CRT 为 233 µm 和 BCVA 为 29 个字母。受试者 #202 在注射后视网膜积液显著消除，CRT 分别在注射后 4 周和 8 周恢复至 162 µm 和 155 µm。从 4 周开始观察到 BCVA 改善了近 15 个字母，并在注射后 8 周随访中持续存在。接受治疗的三名受试者均未观察到与药物相关的严重不良事件。三名患有 nAMD 的受试者在注射 HG202 后，局部和全身不良事件情况均可接受。受试者 #202 在注射 HG202 后 8 周内，BCVA、CRT 和持续性液体排出均有显著改善。尽管只有低剂量组完成了入组，但这项研究为 CRISPR/Cas13 RNA 疗法对人类相对安全提供了基础。截图来源：Insight 数据库新生血管性年龄相关性黄斑变性 (nAMD) 是老年人失明的主要原因，其中血管内皮生长因子 (VEGF) 起着关键作用。频繁玻璃体内注射抗 VEGF 疗法是 nAMD 的一线治疗方法；然而，每次注射仅有效 1-2 个月，并且需要频繁重新给药。尽管临床结果良好，但许多患者在重复给药后会出现持续性液体或复发性渗出，这会导致严重的并发症并降低患者对治疗的依从性，从而导致视力随着时间的推移而丧失。 HG202 是首个进入临床阶段的 CRISPR/Cas13 RNA 编辑疗法，也是唯一针对湿性年龄相关性黄斑变性 (nAMD) 的临床阶段 RNA 靶向治疗。它可以通过单剂量部分降低视网膜中 VEGFA 的 mRNA 表达，减少治疗频率并可能改善临床结果，给湿性年龄相关性黄斑变性（AMD）患者带来了潜在的治疗希望。封面来源：企业 Logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：vvy PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

基因疗法信使RNA临床申请临床研究

100 项与 HG-202 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
年龄相关性黄斑变性	临床1期	-	辉大（上海）生物科技有限公司初创企业	2025-04-01
湿性年龄相关性黄斑变性	临床1期	中国	辉大（上海）生物科技有限公司初创企业	2023-09-06