Glycogen Storage Disease Type III

As several well-funded companies race to make generative AI models that can design new protein therapies from scratch , one small startup has found a new use for existing AI systems: compressing large proteins to better package them in gene therapies or deliver them to hard-to-reach places like the back of the eye. The startup, called ZipBio, has raised $4 million in seed funding for the idea, it told Endpoints News exclusively. “The inspiration came from the compression of technology in the digital world,” CEO Roee Farber said in an interview. Of course, shrinking the structure of a protein and retaining its function isn’t as simple as compressing digital documents into a zip file. The startup is trying to isolate small parts of proteins that are most important for making a drug and shave off the rest. The problem is that the rest of the protein is there for a reason. Removing it can cause the entire thing to collapse. ZipBio’s solution is to use generative AI to create a new backbone that holds that key part of the protein in place. “In the past, nobody succeeded with that. Now it’s something we can do relatively trivially,” Farber said. The company hasn’t published details about how its approach works, but Farber said ZipBio is using and refining publicly available AI models for protein design, rather than creating its own. The startup was founded in 2023, began work on its lead drug just eight months ago, and is already testing it in animals, Farber said. That drug candidate builds on Regeneron’s antibody Eylea as a starting point — an eye therapy that made the company $5.89 billion last year. Eylea inhibits two forms of VEGF, a protein that can spur unwanted blood vessel growth in the eyes. But just blocking the A and B forms of the protein doesn’t fully treat everyone. ZipBio has created a compact inhibitor of VEGF-C and VEGF-D and meshed it with Eylea, using AI to create a hybrid molecule that Farber says is compact enough to travel to the back of the eye, something that a simple fusion of two full antibodies likely wouldn’t do. Clinical trials could begin as soon as 2026. The startup is also working with the French nonprofit Généthon to create a compact version of a protein that’s too big to fit into AAVs — the most common viral vectors used in gene therapy — to treat a rare disease called glycogen storage disorder III, a form of muscular dystrophy. ZipBio’s seed funding was led by NFX, a venture capital firm that invests in tech startups at a seed stage or earlier. MoreVC, which focuses on early-stage Israeli tech startups, also contributed. ZipBio’s team of 12 is currently split between Seattle and Tel Aviv, Israel.

HYOGO, Japan--( BUSINESS WIRE )-- JCR Pharmaceuticals Co., Ltd. (TSE 4552; Chairman and President: Shin Ashida; “JCR”) announced today the completion of the regulatory review by the Pharmaceuticals and Medical Devices Agency (PMDA) for the clinical trial notification for the Phase I study of JR-441 in individuals with mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome type A). JR-441 is a recombinant form of heparan N-sulfatase that is developed using JCR’s proprietary J-Brain Cargo ® blood-brain barrier (BBB)-penetrating technology. JR-441 addresses a significant unmet medical need by crossing the BBB and targeting the neurological symptoms of MPS IIIA within the central nervous system. "MPS IIIA is a rare and life-threatening lysosomal storage disorder for which there are currently no approved treatment options for individuals living with this devastating disease, and there is a dire need to address the neurological signs and symptoms of MPS IIIA,” said Shin Ashida, Chairman and President of JCR Pharmaceuticals. “We are pleased that the PMDA’s review of the Phase I study plan is complete, and that clinical development program is progressing. We are committed to continuing to advance the JR-441 clinical development program with the goal of meeting the unmet medical needs of this patient community. We look forward to sharing updates on the program when they are available.” The European Commission (EC) and the U.S. Food and Drug Administration (FDA) granted JR-441 orphan drug designation (ODD) for the treatment of MPS IIIA. JR-441 is currently being studied in an ongoing Phase I/II clinical trial in Germany (JR-441-101, NCT06095388 ), apart from this Japanese Phase I study. The impact of this announcement on JCR's consolidated financial results for this fiscal year (ending March 2025) is expected to be minor. About Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A) Mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A, is an autosomal recessive disease caused by pathogenic mutations in the SGSH gene, encoding a lysosomal enzyme involved in the degradation of heparan sulfate. The accumulation of heparan sulfate in several types of cells of the body, especially in the central nervous system in the brain, results in severe neurological deterioration, cognitive impairment, mild somatic involvement, and shortened lifespan. About JCR Pharmaceuticals Co., Ltd. JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceuticals company that is expanding possibilities for people with rare and genetic diseases worldwide. We continue to build upon our 49-year legacy in Japan while expanding our global footprint into the US, Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. JCR strives to expand the possibilities for patients while accelerating medical advancement at a global level. Our core values – reliability, confidence, and persistence – benefit all our stakeholders, including employees, partners, and patients. For more information, please visit https://www.jcrpharm.co.jp/en/site/en/ . Cautionary Statement Regarding Forward-Looking Statements This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future.

▎药明康德内容团队报道今日（4月17日），中国国家药监局药品审评中心（CDE）官网公示，赛诺菲（Sanofi）1类新药frexalimab注射液获得两项临床试验默示许可，分别拟开发治疗成人复发型多发性硬化（RMS）、成人非复发性继发进展型多发性硬化（nrSPMS）。公开资料显示，frexalimab是一款靶向CD40L的单克隆抗体。该产品此前已经在治疗多发性硬化的2期临床研究中达到主要终点，研究结果已发表于《新英格兰医学杂志》。截图来源：CDE官网多发性硬化（MS）是一种慢性疾病。MS发生时，免疫系统异常攻击中枢神经系统（脑、脊髓和视神经）中神经细胞的髓鞘（对神经细胞的轴突起到绝缘和支持作用），导致炎症和损伤。这种损伤可能导致一系列症状，包括肌肉虚弱，疲劳和视力困难，最终可能导致残疾。大多数MS患者在20到40岁之间首次出现症状，使该疾病成为年轻成年人非创伤性残疾的主要原因。临床和病理证据表明，CD40/CD40L通路在多发性硬化的发生和进展中起关键作用，可能与外周免疫耐受有关。CD40L通过与其受体CD40的相互作用，在调节T细胞与其他免疫细胞（尤其是B细胞和抗原呈递细胞）之间的相互作用方面发挥着重要作用，从而影响与自身免疫疾病有关的一些重要功能。Frexalimab（SAR441344）是赛诺菲在研的一种新型单克隆抗体。该产品被认为能够阻断适应性（T和B细胞）和先天性（巨噬细胞和树突状细胞）免疫细胞活化和功能所必需的共刺激CD40/CD40L细胞通路，而不会导致淋巴细胞耗竭。截图来源：参考资料[2]今年2月，赛诺菲宣布frexalimab治疗多发性硬化患者的2期试验的积极结果发表于《新英格兰医学杂志》。该研究将129名患有复发型多发性硬化的成人随机分配接受两剂frexalimab中的一剂（高剂量和低剂量组）或匹配安慰剂。在高剂量治疗组中，受试者每4周静脉注射1200毫克frexalimab。在低剂量治疗组中，受试者每2周皮下注射300毫克frexalimab。治疗12周后的分析结果显示，两种剂量的frexalimab均显著降低患者新出现的GdE T1高信号核磁共振成像（MRI）脑部病灶的数量。与安慰剂相比，较高和较低剂量frexalimab组患者的新出现GdE T1病灶数量比率分别为0.11与0.21，即较高和较低剂量的frexalimab分别使新出现的GdE T1病灶数量减少了89%和79%，达成试验主要终点。此外，两种剂量的frexalimab均显著降低患者新发/扩大的T2病变的数量，达成试验次要终点。根据ClinicalTrials官网，赛诺菲已经启动了frexalimab的两项3期临床研究，分别用于治疗成人非复发性继发进展型多发性硬化（nrSPMS）以及复发性多发性硬化（RMS）。除了针对多发性硬化，赛诺菲目前还正在2期临床研究中评估frexalimab治疗其他自身免疫性疾病的潜力，包括干燥综合征、系统性红斑狼疮、1型糖尿病等。参考资料：[1] 中国国家药监局药品审评中心（CDE）官网. Retrieved  Apr 17  , 2024,   from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d[2] Sanofi R&D day. Retrieved December 7, 2023, from https://www.sanofi.com/assets/dotcom/content-app/events/investor-presentation/2023/r-and-d-day-2023/Presentation.pdf[3] Press Release: Phase 2 data published in NEJM show potential of frexalimab as high-efficacy therapy in relapsing MS. Retrieved February 15, 2024 from https://www.sanofi.com/en/media-room/press-releases/2024/2024-02-15-13-00-00-2829933本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。