MECP2

NEW YORK and TRUMBULL, Conn., April 30, 2025 /PRNewswire/ -- Apertura Gene Therapy, a biotechnology company focused on innovative gene therapy solutions, and the Rett Syndrome Research Trust (RSRT), an organization working to cure Rett Syndrome, today announced a collaboration to license Apertura's human transferrin receptor 1 capsid (TfR1 CapX). This partnership aims to advance innovative genetic medicine approaches for the treatment of Rett Syndrome, a rare genetic neurological disorder caused by random mutations in the MECP2 gene on the X chromosome that primarily affect females, causing developmental regression and severe motor and language impairments. Apertura's TfR1 CapX is an intravenously delivered adeno-associated virus (AAV) capsid engineered to bind the transferrin receptor 1(TfR1), enabling efficient delivery of genetic medicines across the blood-brain barrier (BBB). TfR1 is a well-characterized BBB-crossing receptor, broadly and consistently expressed throughout life—even in the context of neurological disease—making it an attractive target for CNS delivery in disorders like Rett syndrome. Developed by Apertura's academic founder, Dr. Ben Deverman, Director of Vector Engineering at the Broad Institute, TfR1 CapX has shown strong CNS selectivity in preclinical studies, achieving over 50% neuronal and 90% astrocyte transduction across multiple brain regions. Because Rett syndrome affects the brain diffusely, broader cellular transduction may correlate with greater symptomatic improvement. "Efficient, safe, and widespread delivery of genetic medicines to the brain is the ultimate goal for treating CNS disorders such as Rett syndrome. Successfully addressing this challenge would dramatically accelerate the development of genetic medicines for Rett and other neurological diseases. My colleagues and I have extensively evaluated advanced delivery technologies, and Apertura's capsid stands out for its impressive CNS biodistribution capabilities," said Monica Coenraads, Founder and CEO of RSRT and parent to an adult daughter with Rett. "We're enthusiastic about integrating this innovative capsid into our internal gene-editing programs and facilitating its adoption for external Rett syndrome programs as well. This collaboration represents a major step forward for patients." Last year RSRT launched the MECP2 Editing Consortium, a collaboration among six labs, developing next-generation genetic medicines for Rett syndrome. The Consortium's editing programs will be utilizing the Apertura capsid to deliver genetic medicine cargoes diffusely across the brain non-invasively. Furthermore, the license allows RSRT to sublicense the capsid for Rett programs. "RSRT has made remarkable progress in advancing Rett syndrome therapies, and Apertura is committed to accelerating this momentum with TfR1 CapX. Our engineered capsid addresses the critical need for more potent and less invasive treatments, significantly benefiting patients and caregivers. This collaboration reflects the innovative efforts of both organizations and serves as a pioneering example of how industry partnerships can rapidly advance vital therapies for patients in need," said Diego Garzón, PhD, Vice President of Corporate Development, Apertura Gene Therapy. "Apertura's TfR1 capsid has the potential to transform treatments for CNS diseases. We are committed to partnering with both for-profit and non-profit organizations to maximize this innovation's impact for patients." About Rett Syndrome Rett syndrome is a rare genetic neurodevelopmental disorder caused by random mutations in the MECP2 gene on the X chromosome. The disorder predominantly affects girls but can also rarely affect boys. Symptoms typically become apparent between the ages of 12 to 18 months. Rett syndrome is devastating as it deprives toddlers of speech, hand use, and normal movement often including the ability to walk. As childhood progresses the disorder brings anxiety, seizures, tremors, breathing difficulties, and severe gastrointestinal issues. While their bodies suffer, it is believed that their cognitive abilities remain largely intact. Although most children survive to adulthood, they require total round- the-clock care. About Rett Syndrome Research Trust The Rett Syndrome Research Trust is a non-profit organization exclusively focused on advancing genetic medicines for Rett syndrome. Multiple clinical trials in gene therapy for Rett syndrome are now underway, all possible because of RSRT-funded research. In 2024 RSRT launched a $40 million initiative, Roadmap to Cures, with a goal to bring three genetic medicines, beyond the current gene therapies, to clinical trials by 2028. RSRT's mission is clear, urgent, and personal: to cure Rett syndrome and transform the lives of the people we love. To learn more, please visit . Follow us on Facebook, Instagram and YouTube. About Apertura Gene Therapy Apertura Gene Therapy is a biotechnology company unlocking new opportunities for treating currently intractable diseases. The company is uniquely positioned to develop genetic medicines to overcome limitations in cellular access, gene expression, pre-existing immunity and manufacturability. Founded in 2021 on technology from the Broad Institute, and with support from Deerfield Management Company, the company is based in New York City. For more information, please visit our website at and follow us on LinkedIn. Contact: Apertura Gene Therapy Diego Garzón [email protected] Rett Syndrome Research Trust Amanda Breeding Scient PR [email protected] SOURCE Apertura Gene Therapy WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Welcome back to Endpoints Weekly! Our team of reporters covered first-quarter earnings results from a handful of companies this week. See below for pharma executives’ comments on tariff exposure, dealmaking and more. We also have an assessment of the industry’s first quarter from Endpoints News’ founding editor John Carroll, who broke down numbers and charts on dealmaking activity, VC investment and more. We’ll be following more Q1 updates next week from Pfizer, Moderna, GSK and others, so stay tuned. And keep an eye out for news from the American Association for Cancer Research Annual Meeting in Chicago, where our reporter Lei Lei Wu is on the ground covering the latest readouts and trends. — Nicole DeFeudis Some of the biggest names in the pharma industry reported their first-quarter earnings this week, including Sanofi, Roche, Merck, Bristol Myers Squibb, Gilead and AbbVie. Tariffs were top of mind for investors , with each company’s executives getting peppered with questions about how President Donald Trump’s trade war would affect the industry. Most opted for a wait-and-see approach , but Roche CEO Thomas Schinecker notably took a proactive stance in warning of a negative impact on dealmaking. Any questions or unknowns about tariffs would make it “more difficult to make financial sense of any M&A deals,” he said Thursday. Roche estimates that four of its medicines make up about 92% of its tariff exposure, though it wouldn’t specify which drugs those are. Here’s a quick rundown of some of the other highlights: FDA Commissioner Marty Makary floated a potential new regulatory pathway for some rare disease treatments. In a SiriusXM interview, Makary highlighted that randomized controlled trials aren’t always feasible for extremely rare diseases. He told Megyn Kelly that drugs could potentially be cleared for use “based on a plausible mechanism” on a “conditional basis,” and the agency would closely monitor patients on the drugs until there’s a clearer signal in the data. He reiterated the pathway in an interview with PBS’ “NewsHour” co-anchor and co-managing editor Amna Nawaz this week. “If you’re treating a condition that only affects 52 kids in the world, we shouldn’t be requiring a randomized controlled trial. We may want to authorize or approve something for that condition based on what I call a plausible mechanism, a plausible scientific mechanism,” Makary said during the interview. Further details remain unclear at this time. The idea echoes work by former CBER Director Peter Marks around accelerated approvals for rare disease gene therapies, as well as a bill from former Sen. Mike Braun (R-IN) and Sen. Kirsten Gillibrand (D-NY) to create a new way for the FDA to grant time-limited provisional approval to rare disease drugs that substantially demonstrate early evidence of safety and efficacy. A Chinese biotech shared preliminary results from the first study to test a CRISPR-based treatment in the brain. Alvin Luk, CEO of HuidaGene Therapeutics, spoke to Endpoints’ Ryan Cross last week about the company’s first clinical trials and its business strategy. What is MECP2 duplication syndrome? It’s a rare neurodevelopmental condition that can cause intellectual disability, movement problems and seizures. HuidaGene gave a low dose of its experimental therapy to a 9-year-old boy with MECP2. Three months later, the boy appeared to have improved eye contact, motor skills and walking ability, and was able to respond to simple directions such as “come to eat” or “go to the bathroom.” The results are still early, but HuidaGene is now considering partnerships that could advance its programs. The company also recently unveiled early results for its experimental CRISPR therapy in Duchenne muscular dystrophy. The DMD and MECP2 therapies were both tested in an investigator-initiated trial, where academic or hospital researchers can move forward with less stringent requirements. But Luk said he plans to take the data to the FDA to get clearance for Phase 1 clinical trials in the US. HuidaGene is working on a broad gene editing toolkit, from Cas12 enzymes for DNA cutting to Cas13 for RNA knockdown to tools for base editing and epigenetic editing. “We can choose which tool is the best for the disease,” Luk said. It was a major factor in his decision to join the company as CEO in 2023. Endpoints’ founding editor John Carroll examined biotech’s first-quarter performance this week, pulling in the numbers and charts from Chris Dokomajilar at DealForma. Carroll notes that despite the XBI falling 27% since Trump won the November election, a massive FDA reorganization and broader HHS layoffs, there are some positive signs under the hood. Most importantly, dealmaking activity remains active, even though IPOs and PIPEs remain cool. Mid- and late-stage assets continue to make attractive takeout options for bigger companies, while licensing deals and other partnerships are holding steady. But a big question remains: Can these trends hold up for the rest of the year as uncertainty lingers from Trump’s tariffs? The number of barely surviving biotechs has reached a crisis level for some investors, and a handful of individuals are looking to do something about it. Nicholas Johnston, a longtime healthcare banker at JP Morgan and Perella Weinberg Partners, recently launched Alis Biosciences, which wants to work with C-suites and boards to make better use of their cash. They estimate over $30 billion in “trapped” capital on the books of an estimated 300 publicly traded biotechs.

全文共2589字预计阅读时长7分钟“中国企业在基因编辑领域已具备与美国同行相当的竞争力，这种趋势只会持续增强。”在CRISPR MEDiCiNE 2025峰会上，参会的美国科学家马克·温伯格如是说。让温伯格有感而发的，是其眼前看到的来自中国生物技术公司辉大基因的两项最新研究结果：1）HG302（hfCas12Max治疗杜氏肌营养不良）：零严重不良反应，无剂量限制性毒性，患儿3个月内即呈现运动功能改善（北极星评估+1分，6分钟步行距离增加60米，4级爬梯时间缩短30秒）。2）全球首款RNA编辑疗法HG204（hfCas13Y治疗MECP2重复综合征）：患儿认知、运动与情绪显著改善，为这一毁灭性儿童神经发育疾病带来曙光。其中，这项针对MECP2重复综合征（一种致死性遗传病）的初步研究成果具有里程碑意义，因为这是首个在大脑内测试的CRISPR疗法！首个在大脑内测试的CRISPR疗法2024年底，医生们将一种实验性CRISPR疗法注入了一名患有MECP2重复综合征的9岁男孩大脑中。所谓MECP2重复综合征，指的是一种罕见的X染色体连锁神经发育障碍，由MECP2基因（甲基化CpG结合蛋白2基因）的额外拷贝（重复或倍增）引起。该基因位于Xq28区域，其过度表达会导致神经系统功能异常，主要影响男性（女性由于X染色体失活机制通常症状较轻）。具体到这位9岁的患者，虽其生理年龄已经达到9岁，但其智力水平相当于11个月大婴儿，临床上表现为智力障碍、运动障碍、语言发育迟缓和缺失、反复呼吸道感染等。辉大基因分享的视频显示，在治疗前，这个男孩需要有人双手搀扶才能勉强行走。他对抛球或堆叠积木等口头指令毫无反应。但四周后，他能够传递皮球；十二周后，他的步态明显改善，积木堆叠动作也更为灵巧。这项针对MECP2重复综合征（一种致死性遗传病）的初步研究成果具有里程碑意义：这不仅是首个在大脑内测试的CRISPR疗法。更值得注意的是，主导这项突破的是一家名不见经传的中国生物技术公司——辉大基因。据报道，辉大基因采用独特的Cas13Y酶技术，通过调控mRNA而非DNA来精准平衡MECP2基因表达——该基因过度表达会导致当前病症，而表达不足则引发雷特综合征。除此之外，辉大基因还在会议上公布了针对杜氏肌营养不良症（DMD）的两例CRISPR治疗初步数据。辉大基因公开资料显示，在HG302项目中，他们通过单个病毒载体将高保真Cas12（hfCas12Max）和靶向人DMD基因第51号外显子剪接供体（SD）位点的CRISPR RNA递送到肌肉中。该位点将被HG302破坏，从而允许第51号外显子跳跃，形成从第50到53号外显子的正确开放阅读框，恢复功能性肌营养不良蛋白的表达，进而改善肌肉功能。目前，虽然该疗法需要超高剂量（数万亿病毒颗粒），但已治疗的两名患儿暂时均未出现严重不良反应。首例患者治疗后6分钟步行测试距离增加55米，运动功能评估也有改善。且早在2024年初，美国FDA便已授予HG302孤儿药资格认定（ODD），用于治疗DMD。辉大基因：能否成为基因编辑领域新黑马？辉大基因此番崛起正值美国科学界面临研发经费削减、资本避险情绪升温之际。且与中国创新药目前高昂的发展势头高度一致。公开信息显示，辉大基因由杨辉、姚璇等人于2018年创立，致力于基因治疗药物的研发，长期目标是利用基因编辑技术治疗遗传病以及威胁人类健康的慢性疾病。该公司CEO陆英明（Alvin Luk）曾在拜耳、渤健等跨国药企担任高管，曾带领团队在神经、眼科和肌肉疾病领域持续突破。目前，辉大基因已累计融资1.32亿美元，正寻求2700-4000万美元C+轮融资用于渐冻症、阿尔茨海默病等新项目。外媒文章指出，与多数美国同行专注单一技术不同，辉大基因建立了包含Cas12、Cas13、碱基编辑和表观遗传编辑在内的全技术平台。“我们可以为不同疾病选择最佳工具。”陆英明表示，这正是他加入这家公司的关键原因。但就基因编辑疗法的研发而言，仍面临不少未解决的现实难题。一方面，很多基因编辑疗法的在研适应症多为罕见病，患者少，难以满足统计需求。另一方面，基因编辑疗法对DNA/RNA的编辑具有永久性，仍存在很多未知风险概率。陆英明坦言：“我们联系了至少10家医院，有的没听说过CRISPR，有的因2018年'基因编辑婴儿'事件心存顾虑。”基于重重困境，合作共赢是目前像辉大基因这样的公司最好的选择之一。采访中，陆英明透露，公司战略聚焦于技术授权或与大型药企合作。小结就在2月初，STAT News资深遗传学领域记者Jason Mast在采访了75位投资者、高管、分析师和科学家后得出一个结论：The CRISPR companies are not OK。后来，先是蓝鸟生物卖身，后又是福泰制药终止基因疗法相关合作、辉瑞停止相关管线等。一个个失败的案例似乎对这篇文章的结论做出了印证。不过，值得一提的是，从2024年CGT领域的融资事件来看，行情整体在回暖。2024年共28家聚焦细胞疗法的新锐企业获得共约12.1亿美元的早期融资，超越2023年（11.54亿美元）。而就2025年这几个月发生的事情来看，随着行业整体看好情绪上涨，或许类似辉大基因这样的公司仍有大施拳脚之地。点击预约，观看FDA近日大事件回放~参考资料：1.各公司官网2.China startup injects CRISPR therapy into the brain for the first time3.其他公开资料图片来源：AI版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn点击这里，查看更多精彩!