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SHANGHAI, Sept. 4, 2024 /PRNewswire/ -- YolTech Therapeutics, a clinical-stage in vivo gene editing company, announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) to YOLT-203 for the treatment of primary hyperoxaluria type 1 (PH1) in September. Earlier that month, YOLT-203 received Rare Pediatric Disease Designation (RPDD) from the FDA. After reviewing YolTech's submission, the FDA determined that the therapy is not only appropriate for primary hyperoxaluria type 1 (PH1), but also applicable to the broader category of primary hyperoxaluria (PH). As a result, the designations were granted for PH, reflecting the expanded scope of the therapy's potential impact. These dual designations underscore the transformative potential of YOLT-203 to address this rare and life-threatening genetic disorder. About Primary Hyperoxaluria and PH1 Primary hyperoxaluria (PH) is a rare autosomal recessive genetic disorder in which excessive oxalate production in the liver causes kidney stone formation, progressive renal damage, and systemic oxalosis. The most common subtype of PH, primary hyperoxaluria type 1 (PH1), results from dysfunction of alanine-glyoxylate aminotransferase (AGT) due to mutations in the AGXT gene. In the absence of intervention, most patients progress to end-stage renal disease (ESRD), requiring intensive hemodialysis and often a dual liver-kidney transplant to correct the metabolic defect and address organ failure. About YOLT-203 YOLT-203 is an innovative investigational in vivo gene editing therapy designated to provide a one-time, potentially curative treatment for primary hyperoxaluria type 1 (PH1). YOLT-203 permanently reduces excessive oxalate production in PH1 by deactivating the HAO1 gene through YolTech's proprietary YolCas12™ system, a novel CRISPR/Cas enzyme identified through the High-Throughput Evolution Platform (HEPDONE®). YOLT-203 is administered through intravenous infusion of liver-targeted lipid nanoparticles (LNPs) encapsulating YolCas12 mRNA and a guide RNA (gRNA) targeting the HAO1 gene. YOLT-203 also represents a historic milestone as the first in vivo gene editing therapy to enter clinical trial globally for a pediatric rare disease. Clinical Development and Early Results The investigator-initiated clinical study of YOLT-203 began on August 5, 2024, with the first adult patient dosed, followed by the first pediatric patient on August 20, 2024. Early data from preclinical and initial clinical studies have demonstrated promising reductions of over 90% in blood oxalate levels, with no dose-limiting toxicities (DLTs) or severe adverse events (SAEs) leading to treatment interruptions observed to date. Significance of FDA Designations The Rare Pediatric Disease Designation (RPDD) program encourages the development of new drugs and biologics for rare pediatric conditions. This designation makes YolTech eligible to receive a priority review voucher (PRV) upon potential FDA approval of YOLT-203. Similarly, the Orphan Drug Designation (ODD) program provides benefits including tax credits, exemption from certain FDA fees, and seven years of market exclusivity upon regulatory approval. About YolTech Therapeutics YolTech Therapeutics is a clinical-stage in vivo gene editing company committed to pioneering the next generation of precision genetic medicines. Our approach combines innovative gene editing technologies with an advanced lipid nanoparticle (LNP) delivery system, creating a versatile platform designed to address a wide range of serious diseases. Central to our mission is the development of internal capabilities, including end-to-end manufacturing, to ensure the highest standards of quality and scalability. Our lead candidate, targeting ATTR, marks a significant milestone as China's first LNP-mediated in vivo gene editing therapy to enter clinical development. With promising early clinical outcomes, YolTech is also advancing therapies for familial hypercholesterolemia (FH) and primary hyperoxaluria type 1 (PH1). As a company dedicated to transforming the treatment landscape, YolTech continues to push the boundaries of what is possible in gene editing. For more information, visit: or follow YolTech on LinkedIn: YolTech Therapeutics. Contacts Colin LIN Business Development & Investor Relations [email protected] +86 180 2100 7750 SOURCE YolTech Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Dec. 19, 2024 -- Arbor Biotechnologies™, a biotechnology company discovering and developing the next generation of genetic medicines, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for ABO-101, a novel gene editing therapeutic designed to address primary hyperoxaluria type 1 (PH1). The redePHine Phase 1/2 study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ABO-101 in both adult and pediatric patients with PH1. “We are thrilled to advance ABO-101 to the clinic as we believe it has the potential to be a first-in-class treatment for PH1, a rare disease with a high unmet need, and reinforces the promise of our precisely tailored gene editing approach,” said Dan Ory, M.D., Chief Medical Officer of Arbor. “ABO-101 is supported by a strong suite of preclinical data demonstrating specific and durable in vivo editing of HAO1 and corresponding, therapeutically relevant reductions in urinary oxalate in PH1 disease models.” ABO-101 is a liver-targeted gene editing therapeutic in development for the treatment of primary hyperoxaluria type 1 (PH1). PH1 is a rare genetic disorder in which enzyme deficiencies in the liver lead to the overproduction and buildup of oxalate, resulting in kidney stones eventually leading to end stage kidney disease and systemic oxalosis. ABO-101 is designed to knock down HAO1 gene expression in the liver, thereby providing durable reduction in oxalate production. “The FDA approval of the ABO-101 IND marks a significant milestone for the hyperoxaluria community. At OHF, we are committed to partnering with industry leaders to advance care, research, and patient-focused drug development for hyperoxaluria. Arbor’s innovative CRISPR-based approach represents a groundbreaking opportunity in genomic medicine, with the potential to transform the lives of patients with PH1,” said Kim Hollander, Executive Director of The Oxalosis and Hyperoxaluria Foundation. “The initiation of this study marks an important milestone both for patients with PH1 and in the growth of our company as we begin advancing our pipeline of first-in-class programs into the clinic,” said Devyn Smith, CEO of Arbor. “There is a tremendous need for innovative approaches to treat genetic conditions – from ultra-rare to the most common genetic diseases – and we’re excited for the potential of our next-generation genetic medicines that can address a vast spectrum of devastating diseases. I applaud the hard work of our team at Arbor for getting us to this stage.” ABO-101 is a novel, investigational gene editing medicine designed to be a one-time treatment that results in a permanent loss of function of the HAO1 gene in the liver to reduce PH1-associated oxalate production. ABO-101 consists of a lipid nanoparticle (LNP), licensed from Acuitas Therapeutics, encapsulating messenger RNA expressing a novel Type V CRISPR Cas12i2 nuclease and an optimized guide RNA which specifically targets the human HAO1 gene. Arbor Biotechnologies™, a next-generation gene editing company based in Cambridge, MA, is advancing a pipeline of novel gene editing therapeutics to address a wide range of genetic conditions – from the ultra-rare to the most common genetic diseases. The company’s unique suite of optimized gene editors goes beyond the limitations of early editing technologies to unlock access to new gene targets and has fueled a robust pipeline of first-in-class assets focused on diseases of high unmet need. With Arbor’s lead program, ABO-101 for the treatment of primary hyperoxaluria type 1, progressing into clinical trials, the company continues to focus their research and development efforts on genomic diseases of the liver and CNS for which there are no existing functional cures. For more information, please visit: arbor.bio. The content above comes from the network. if any infringement, please contact us to modify.

文章解读+创新点拓展，为您带来科研新体验～ 导读 随着全球儿童和青少年肥胖率的不断攀升，其带来的健康问题日益受到关注。肥胖不仅是体脂异常积累的结果，更是心血管代谢疾病的重要危险因素。近日，一项发表于《Nature Medicine》杂志上的研究《Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity》，通过脂质组学技术揭示了肥胖儿童和青少年中可调节的心血管代谢风险特征，为肥胖管理提供了新的视角。本文将详细介绍该研究的技术方法及其临床应用价值。 研究背景 儿童和青少年期肥胖是一个逐渐发展的慢性病，可能导致严重的代谢并发症，如胰岛素抵抗、非酒精性脂肪肝等。尽管已有大量研究探讨了肥胖与心血管代谢风险之间的关系，但对于肥胖个体中具体哪些生物标志物可以作为干预靶点的研究仍然有限。本研究旨在利用脂质组学技术，识别肥胖儿童和青少年中与心血管代谢风险相关的脂质特征，并评估这些特征是否可以通过生活方式干预得到改善。 研究设计与结果 研究团队首先在一个横断面研究中收集了958名超重或肥胖儿童和青少年以及373名正常体重儿童和青少年的血样。这些样本来自丹麦的HOLBAEK研究，包括一个肥胖诊所队列和一个基于学校的人群队列。所有参与者均经过详细的临床评估，包括身高、体重、腰围、血压和生化指标的测量。研究团队采用了基于质谱的脂质组学技术，对所有样本血浆脂质进行了非靶向脂质组学分析，并探究了血浆脂质与心血管代谢风险以及与肥胖/超重的相关性。 在此基础上，为了验证这些脂质特征是否可以通过干预得到改善，并进一步降低心血管代谢风险，研究团队实施了一个家庭为基础的个性化管理项目，对上述研究中186名肥胖儿童和青少年进行了非药物干预和随访。 这些结果表明，通过生活方式干预，可以显著改善肥胖儿童和青少年的脂质谱型，从而降低心血管代谢风险。 图1：研究设计概览 图2：与超重/肥胖相关的血浆脂质组概述 在调整了年龄和性别后，三种体重状态（正常体重、超重和肥胖）之间的脂质谱型呈现出逐渐变化的趋势。在227种注释的脂质种类中，有142种在正常体重、超重和肥胖之间表现出显著差异（P < 5% 错误发现率（FDR））。两两比较显示，正常体重和肥胖之间有121种脂质存在显著差异，超重和正常体重之间有43种差异，超重和肥胖之间有60种差异。 在13个脂质大类中，有87种脂质出与体重有显著相关性，其中52种呈正相关，35种呈负相关，且这些相关性与年龄和性别无关（P < 5% FDR）。具体而言，20%的神经酰胺（Cer）、33%的鞘磷脂（SM）、47%的甘油三酯（TG）、所有二酰基甘油酯（DG）和40%的脂肪酸呈正相关。相反，大多数甘油磷脂，包括33%的N,N-二甲基磷脂酰乙醇胺（dMePE）和60%的溶血磷脂酰乙醇胺（LPE），显示出负相关。此外，磷脂酰胆碱（PC）、磷脂酰乙醇胺（PE）和磷脂酰肌醇（PI）表现出更复杂的双向趋势：14%和20%的PC、25%和17%的PE以及12%和38%的PI分别显示出显著的正向和负向相关性。 图3：肥胖与年龄相关的脂质种类变化 接着，该团队研究了不同体重组脂质类型和水平变化与年龄的关系，发现26脂质类型展现出显著的体重-年龄交互作用。在正常体重组中，溶血磷脂（如LdMePE(16:0/0:0)、LPC(14:0)）随着年龄的增长显著增加，而在超重/肥胖组中增加不明显。相反，多不饱和脂肪酸（如FA(20:4)、FA(22:6)）在超重/肥胖组中随着年龄的增长显著减少，而在正常体重组中无显著变化。此外，甘油三酯水平在超重/肥胖组中随着年龄的增长显著增加，而在正常体重组中无显著变化。这些结果表明，肥胖与年龄之间的相互作用对脂质代谢产生了显著影响，进一步强调了早期干预的重要性。 图4：脂质种类与心血管代谢风险的关联 然后，研究者分析了脂质类别与心血管代谢风险特征的相关性，发现了135种脂质与心血管代谢风险特征至少有一种显著相关，207种脂质与心血管代谢特征至少有一种显著相关。34种心血管代谢风险相关脂质（Cer、SM、PE、PI）与连续心血管代谢特征相关。其中，特定的Cer与肝脏相关性状（肝脏脂肪百分比、ALT、AST和GGT）、传统血脂（LDL-C、TC和TG）和血糖性状（C肽、HOMA-IR、胰岛素和血糖）、胰高血糖素和GLP-1呈正相关。SM与TG、肝脏和血糖特征、瘦素/脂联素比值和GLP-1呈负相关。此外，PI和PE与肝脏和血糖特征、瘦素：脂联素比值和GLP-1呈正相关。PI还与较高的hs-CRP、胰高血糖素和舒张压标准差水平相关。体重会影响这其中25种脂质与14种心血管代谢特征之间的相关性，特别是在儿童和青少年中的超重和肥胖人群，Cer、SM、PE和PI与ALT和GGT之间、SM与胰岛素以及PI与hs-CRP、瘦素、胰高血糖素、GLP-1和舒张压标准差之间的相关性增强。 在此基础上，研究团队开发了一个由三种脂质组成的模型（PI(32:1)、PE(36:1)和Cer(d42:0)），用于预测肝脏脂肪变性，其预测能力与肝酶相当。通过Spearman相关分析，研究团队还发现多种脂质类型与心血管疾病和炎症标志物之间存在显著相关性，比如Cer、PE和PI与心血管疾病标记物相关，包括FGF21、PRSS8、 SPON2、HAOX1、LEP和ADM，这些结果进一步证实了这些脂质物种在心血管代谢风险中的重要作用。 中介分析发现83种肥胖相关的脂质可能介导了肥胖对19种心血管代谢特征的影响。具体而言，TG (52：1) 在各种代谢性心血管疾病特征之间表现出部分中介效应。此外，SM、LPE和LPC被发现对肥胖与糖代谢特征之间的关联具有负向中介作用。 图5 ：脂质介导的肥胖与心血管代谢风险的关联 研究者为了进一步研究脂质变化是否与肥胖管理降低心血管代谢风险的作用有关，对186名儿童和青少年进行了中位干预时间为1.1年的肥胖管理。肥胖管理显著改善了BMI和传统血脂等指标，同时，PC、LPC和LPE等44种脂质显著增加（P < 0.05），而Cer、SM和TG等23种脂质显著减少。BMI SDS减少与11种心血管代谢特征和70种脂质的变化相关，有216条路径具有显著的间接效应，占总路径数的85%，其中介效应为23%。65种脂质的变化显著地介导了BMI SDS减少与传统脂质变化的关系，其中介效应从7%到60%不等。这些结果表明，脂质在肥胖与心血管代谢风险之间的关系中起着重要的中介作用，通过脂质组学技术可以更全面地评估脂质在肥胖管理中的作用，为临床管理和干预提供科学依据。 拓展延伸 脂质组学在其他科研领域的应用： 1. 心血管疾病研究 ● 动脉粥样硬化：脂质组学技术可以帮助识别与动脉粥样硬化相关的脂质分子，如氧化低密度脂蛋白（ox-LDL）和磷脂酰胆碱（PC）。这些脂质分子在动脉粥样硬化的发生和发展中起关键作用，通过脂质组学分析可以揭示其具体的代谢途径和调控机制。 ● 心肌梗死：脂质组学可以用于研究心肌梗死后脂质代谢的变化，帮助发现新的生物标志物和治疗靶点。例如，研究发现心肌梗死后血浆中某些鞘磷脂水平显著升高，这可能与炎症反应和细胞凋亡有关。 2. 代谢性疾病研究 ● 2型糖尿病：脂质组学技术可以帮助识别2型糖尿病患者的特异性脂质谱型，如高浓度的游离脂肪酸（FFAs）和低浓度的长链酰基肉碱（LCACs）。这些脂质特征可以作为早期诊断和预后的生物标志物。 ● 非酒精性脂肪肝病（NAFLD）：脂质组学可以揭示NAFLD患者中脂质代谢的异常，如高浓度的甘油三酯和低浓度的磷脂。通过脂质组学分析，可以发现新的治疗靶点，如抑制特定脂质合成酶的活性。 3. 癌症研究 ● 乳腺癌：脂质组学技术可以帮助识别乳腺癌患者中特异性的脂质谱型，如高浓度的磷脂酰胆碱（PC）和低浓度的溶血磷脂酰胆碱（LPC）。这些脂质特征可以作为早期诊断和预后的生物标志物。 ● 肺癌：脂质组学可以揭示肺癌患者中脂质代谢的异常，如高浓度的鞘磷脂和低浓度的磷脂酰乙醇胺（PE）。通过脂质组学分析，可以发现新的治疗靶点，如抑制特定脂质合成酶的活性。 4. 神经退行性疾病研究 ● 阿尔茨海默病：脂质组学技术可以帮助识别阿尔茨海默病患者中特异性的脂质谱型，如高浓度的胆固醇和低浓度的磷脂酰丝氨酸（PS）。这些脂质特征可以作为早期诊断和预后的生物标志物。 ● 帕金森病：脂质组学可以揭示帕金森病患者中脂质代谢的异常，如高浓度的鞘磷脂和低浓度的磷脂酰肌醇（PI）。通过脂质组学分析，可以发现新的治疗靶点，如抑制特定脂质合成酶的活性。 5. 免疫系统研究 ● 自身免疫性疾病：脂质组学技术可以帮助识别自身免疫性疾病患者中特异性的脂质谱型，如高浓度的磷脂酰胆碱（PC）和低浓度的溶血磷脂酰胆碱（LPC）。这些脂质特征可以作为早期诊断和预后的生物标志物。 ● 感染性疾病：脂质组学可以揭示感染性疾病患者中脂质代谢的异常，如高浓度的甘油三酯和低浓度的磷脂。通过脂质组学分析，可以发现新的治疗靶点，如抑制特定脂质合成酶的活性。 临床应用与展望 这项研究不仅为我们提供了新的视角来理解肥胖与心血管代谢风险之间的关系，还为临床实践提供了实用的工具和技术支持。希望未来能有更多的研究继续深入这一领域，为改善儿童和青少年的健康状况做出更大的贡献。 注：本文旨在介绍医学研究进展，不做治疗方案推荐。如有需要，请咨询专业临床医生。 参考文献 Huang Y, Sulek K, Stinson SE, Holm LA, Kim M, Trost K, Hooshmand K, Lund MAV, Fonvig CE, Juel HB, Nielsen T, Ängquist L, Rossing P, Thiele M, Krag A, Holm JC, Legido-Quigley C, Hansen T. Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity. Nat Med. 2024 Sep 20.  点击下方「阅读原文」，前往梅斯官网查询更多相关课程和实验技术服务支持~