Yoltech Therapeutics Co., Ltd.

SHANGHAI, April 28, 2025 /PRNewswire/ -- YolTech Therapeutics Co.,Ltd, a clinical-stage in vivo gene editing company committed to pioneering the next generation of precision genetic medicines, announced promising interim clinical data from an investigator-initiated trial (IIT) of YOLT-101 (NCT06458010), and the data has been published on medRxiv. YOLT-101 is an investigational in vivo base editing therapy for the treatment of heterozygous familial hypercholesterolemia (HeFH). Clinical data demonstrate that YOLT-101 can safely and effectively reduce low-density lipoprotein cholesterol (LDL-C) levels in HeFH patients with a single administration. As a next-generation gene-editing therapy, YOLT-101 represents a breakthrough in lipid-lowering treatment – moving beyond daily pills and regular injections, and opening a new era of "one-time treatment for lifelong LDL-C reduction." YOLT-101 is a next-generation in vivo base-editing therapeutic independently developed by YolTech. It features the novel, proprietary adenine base editor, YolBE—specifically hpABE5—which consists of nCas9 and a newly discovered deaminase derived from Hafnia paralvei. For delivery, it utilizes a new lipid nanoparticle (LNP) formulation. Unlike traditional CRISPR/Cas9 systems that rely on inducing DNA double-strand breaks (DSBs), hpABE5 enables precise single-base editing without generating DSBs, thereby significantly reducing the risks of chromosomal abnormalities and off-target effects. Extensive preclinical studies have demonstrated its excellent genome editing safety profile. The in vivo base-editing therapy is delivered via intravenous infusion and selectively internalized by hepatocytes, where it induces a precise nucleotide conversion within the PCSK9 gene. This targeted edit disrupts PCSK9 protein expression, leading to enhanced uptake of LDL-C by LDL receptor on hepatocyte surfaces and finally resulting in a marked reduction in plasma LDL-C levels. Study Design of the IIT This is an open-label clinical trial conducted in patients with HeFH. The primary objective is to evaluate the safety and tolerability of YOLT-101, while also aiming to explore preliminary efficacy and pharmacodynamics. As of March 15, 2025, a total of 6 subjects have been enrolled: 1 in the 0.2 mg/kg cohort, 2 in the 0.4 mg/kg cohort, and 3 in the 0.6 mg/kg cohort. All subjects have completed at least 24 weeks of safety follow-up, with the longest reaching 36 weeks. Safety and Tolerability YOLT-101 has shown good safety and tolerability. As of March 15, 2025, no serious adverse events (SAEs), dose-limiting toxicity (DLT) events, or Grade ≥3 adverse events (according to CTCAE v5.0) were observed in any dose group. All enrolled subjects are under follow-up as scheduled. The most common treatment-related adverse event was transient infusion-related reactions (5/6, 83.3%), with a manifestation of fever that resolved within 24 hours. Mild elevations in liver enzymes (3/6, 50.0%) were reported, which emerged on Day 4-7 following administration and rapidly alleviated usually after 7 days. All these patients did not show any relevant symptoms, and their plasma bilirubin levels (important indices for liver function) remained within normal limits throughout. No clinically significant changes were observed in other laboratory parameters. Efficacy and Pharmacodynamics LDL-C levels demonstrated a dose-dependent reduction following administration. Baseline LDL-C was 4.9 ± 0.6 mmol/L. In the 0.4 mg/kg and 0.6 mg/kg cohorts, sustained reductions in LDL-C were observed as early as Week 1 post-administration, reaching a maximal effect by Week 4. In the 0.6 mg/kg group, mean LDL-C level decreased by around 50% through the last follow-up with acquired data compared to baseline. The subject with the greatest response showed an LDL-C level of approximately 1 mmol/L (maximal percent change from baseline over 74%), and the efficacy has sustained for over 6 months following single-dose infusion. Pharmacodynamic data showed consistent trends, with plasma PCSK9 protein levels decreasing by over 70% from baseline starting at Week 4 in the 0.6 mg/kg group (maximal individual reduction reached 87%). Notably, all enrolled subjects in this study were HeFH patients. PCSK9-targeting therapies typically show reduced efficacy in this population compared to with general hypercholesterolemic population. This suggests that YOLT-101 may demonstrate even greater lipid-lowering potential in the general hypercholesterolemic population. In summary, YOLT-101 exhibits favorable safety and tolerability in HeFH patients, with adverse events being mild and transient. Both pharmacodynamic (PCSK9) and efficacy (LDL-C) outcomes in the 0.4 mg/kg and 0.6 mg/kg groups showed durable, dose-dependent reductions. These results support the potential of YOLT-101 to achieve "single-dose, lifelong lipid lowering." "We are dedicated to revolutionizing traditional approaches to cardiovascular disease through next-generation base editing technology and groundbreaking single-dose treatment," said Dr. Yuxuan Wu, co-founder and CEO of YolTech Therapeutics. " Patients with heterozygous familial hypercholesterolemia (HeFH) suffer from a lifelong, genetically driven impairment in LDL-C metabolism, resulting in markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. This population is at exceptionally high risk for premature atherosclerotic cardiovascular diseases. Current lipid-lowering therapies rely heavily on long-term, continuous administration. However, once treatment is discontinued, LDL-C levels rebound. These regimens are frequently hindered by poor patient adherence and drug intolerance—highlighting a critical unmet need for more durable, patient-friendly therapeutic solutions. Current clinical data of YOLT-101 demonstrates a single YOLT-101 administration can lead to significant and durable reductions in LDL-C levels. By precisely editing key genes regulating LDL-C levels in the liver, YOLT-101 has the potential to be a transformative 'one-time treatment, lifelong cure' therapy. We look forward to further confirming its safety and efficacy in larger-scale clinical studies and conferring benefits to patients worldwide." About Familial Hypercholesterolemia (FH) Familial hypercholesterolemia (FH) is caused by mutations in LDL metabolism-related genes (LDLR, APOB, PCSK9). As a result, patients with FH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). The global prevalence of FH is 1:200-1:250, affecting a total of ~34 million people worldwide. Current FH management strategies include lifestyle modifications, lipid-lowering medications, lipoprotein apheresis, and liver transplantation. The standard of treatment involves pharmacotherapy, with most patients receiving a triple regimen of statins, ezetimibe, and PCSK9 inhibitors. However, current therapies have significant limitations including suboptimal efficacy, intolerable side effects, and poor long-term adherence. These challenges underscore the urgent need for novel, durable therapies to address the lifelong treatment burden of FH. About YolTech 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. 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关注并星标CPHI制药在线4月17日，中国国家药品监督管理局药品审评中心（CDE）官网公示信息显示，尧唐生物（YolTech Therapeutics）研发的1类新药YOLT-101注射液临床试验申请获正式受理。通过CDE官网信息查询确认，此次申报为该产品在中国首次提交IND申请。1. YOLT-101注射液的创新性和疗效家族性高胆固醇血症（FH）是一种常染色体（共）显性遗传病，其发病机制与低密度脂蛋白受体（LDLR）介导的肝脏LDL代谢相关基因发生致病性突变密切相关。临床特征主要表现为血清低密度脂蛋白胆固醇（LDL-C）水平显著升高，以及皮肤/腱黄色瘤的出现。目前针对这种遗传病的治疗手段包括生活方式调整、降血脂药物治疗、脂蛋白血浆置换及肝移植手术等。其中，降血脂药物是最主要的治疗方式。临床对家族性高胆固醇血症患者常采用他汀类药物、依折麦布联合PCSK9抑制剂的三联疗法，但现有治疗手段下，患者仍面临疗效不佳、药物副作用、需终身用药导致依从性差等诸多挑战。YOLT-101注射液是尧唐生物在研的一款靶向PCSK9基因的体内碱基编辑药物。其采用腺嘌呤碱基编辑器YolBE®与新型脂质纳米颗粒（LNP）递送系统。有别于传统CRISPR/Cas9技术依赖的DNA双链断裂机制，YolBE®能够在避免DNA双链断裂的情况下完成单碱基精确编辑。图注：YOLT-101的作用原理（来源：尧唐生物）通过临床前研究验证，该技术在显著降低染色体异常及脱靶风险的同时，展现出优异的基因组编辑安全性。这种安全性优势使其在心血管疾病等常见病症的治疗中更具应用潜力。研究者发起的临床研究（IIT）数据显示，YOLT-101表现出良好的安全性及耐受性。截至2025年1月31日，各剂量组均未出现严重不良事件（SAE）、剂量限制性毒性（DLT）事件，亦无达到CTCAE v5.0标准≥3级的不良事件，且无受试者因不良事件退出研究。从疗效来看，用药后DL-C水平下降呈现明确的剂量依赖性特征。所有纳入疗效评估的受试者均已完成至少16周的随访观察：中、高剂量组在给药后第1周即出现LDL-C水平下降趋势，至第4周时，高剂量组受试者LDL-C最高降幅接近80%，充分体现了YOLT-101注射液对家族性高胆固醇血症患者的显著降血脂效果。2. 体内基因编辑药物的巨大潜力体内基因编辑药物正凭借其“一次治疗、长期有效”的独特优势，重塑人类对遗传疾病的治疗认知。尧唐生物聚焦于研发基于mRNA-LNP递送系统的体内基因编辑药物。公司依托多个技术创新平台，成功开发出新一代基因编辑器YolCas™与碱基编辑器YolBE®，并自主研发出具有知识产权的新型脂质纳米颗粒YOL-LNPs®，显著提升了体内递送效率。图注：尧唐生物核心技术路径YOL-LNPs®实现体内编辑，递送效率高于行业基准数倍（来源：尧唐生物）这种DNA层面的永久性干预，不仅突破了现有药物依赖持续给药的局限，更开启了从“对症治疗”到“对因治愈”的医学革命。尧唐生物首个针对转甲状腺素蛋白淀粉样变性（ATTR）的体内基因编辑药物于2024年3月获CDE批准开展临床试验，并于2024年6月完成首例患者入组，这标志着国内首个由LNP介导的体内基因编辑药物正式进入临床阶段。图注：尧唐生物的研发管线（来源：尧唐生物）2024年8月27日，尧唐生物与信立泰正式签订协议，就其自主研发的PCSK9靶点碱基编辑药物YOLT-101在中国内地的开发及商业化达成合作，总交易金额近10.35亿元人民币。当前全球范围内仅有少数企业进入基因编辑治疗的临床阶段，中国企业通过技术创新与资本赋能，已在体内基因编辑赛道跻身国际第一梯队。随着临床研究的推进，这类药物有望逐步解决遗传病、代谢病等领域的未满足医疗需求，展现出覆盖千万患者的巨大市场价值与技术辐射潜力。结语IYOLT-101注射液ND申请获CDE受理，是中国体内基因编辑药物研发的重要突破。其依托YolBE与LNP技术实现单碱基精准编辑，临床前及临床研究显示YOLT-101可显著降低LDL-C水平，且安全性高。它为家族性高胆固醇血症患者带来新的选择，这也预示着“一次治疗”模式正在逐步迈向现实，前景广阔。参考来源：1. 尧唐生物官网2. CDE官网END【企业推荐】领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

扫描二维码即可下载《数图药讯》2025年4月第16期目   录行业政策1.工业和信息化部办公厅：关于发布首批中国消费名品名单的通知-推动医药品牌发展2.国家卫健委：基层司召开2025年基层卫生健康综合试验区建设工作推进会3.国家药监局：关于18批次化妆品检出禁用原料的通告（2025年第13号）4.福建省医保局：关于印发单列门诊统筹支付医保药品目录（2024年版）的通知5.黄山市医保局：关于公布安徽省2024年度中成药集中带量采购中选结果的通知6.浙江省医保局：全省三级医疗机构谈判药品配备情况一览表(2025年第一季度)7.上海阳光医药采购网：关于公布2025年2月药品挂网公开议价采购监管品种名单的通知行业动态1. 药讯动态：重磅获批2. 药讯动态：重磅临床3. 药企动态：市场动态零售行业动态河北省：全省药店，开始「双码绑定」本周总结政策解读1、工业和信息化部办公厅：关于发布首批中国消费名品名单的通知-推动医药品牌发展为全面贯彻党的二十届三中全会精神，加快落实全国新型工业化推进大会工作部署，贯彻实施中办、国办《提振消费专项行动方案》，根据《工业和信息化部办公厅关于分级打造中国消费名品方阵的通知》（工信厅消费函〔2024〕369号），经企业申报、省级工业和信息化主管部门初审推荐、专家评审和网上公示，工业和信息化部确定了首批中国消费名品名单，现予以公布。在首批93个中国消费名品中，医药行业13家企业入选，名单涵盖历史经典、时代优品、潮流新锐三大维度。具体信息请登录中华人民共和国工业和信息化部官网查看。附件：1.首批中国消费名品名单.pdf2.中国消费名品成长企业名单.pdf相关文件请扫描上方二维码查看2、国家卫健委：基层司召开2025年基层卫生健康综合试验区建设工作推进会国家卫生健康委基层司在山东省寿光市召开2025年基层卫生健康综合试验区建设工作推进会，交流典型做法，宣讲深化医改政策，部署安排下一步重点工作。会议指出，2024年各试验区聚焦重点领域和关键环节，大胆探索、创新突破，在体制机制创新、服务能力提升、资源整合优化等方面取得了明显成效。会议强调，2025年是试验区建设的第五年，要结合试验区重点工作要求，以更加深入的改革、更加务实的举措，落实重点任务、推动资源汇聚、加强系统集成、加大宣传推广、持续监测评价，充分发挥专家支持作用，推动试验区建设再上新台阶。具体信息请登录国家卫健委官网查看。3、国家药监局：关于18批次化妆品检出禁用原料的通告（2025年第13号）在2024年国家化妆品抽样检验工作中，经黑龙江省药品检验研究院等单位检验，产品标签标示名称为妙龄妍亮喵喵亮肤面膜等18批次化妆品不符合规定，检出《化妆品安全技术规范（2015年版）》中规定的禁用原料。根据《化妆品监督管理条例》《化妆品生产经营监督管理办法》《化妆品抽样检验管理办法》，国家药品监督管理局要求北京市、上海市、浙江省、广东省药品监督管理部门对上述不符合规定化妆品涉及的备案人、受托生产企业依法立案调查，责令相关企业立即依法采取风险控制措施并开展自查整改。具体信息请登录国家药监局官网查看。附件：18批次检出禁用原料的化妆品信息.doc相关文件请扫描上方二维码查看4、福建省医保局：关于印发单列门诊统筹支付医保药品目录（2024年版）的通知为贯彻落实《国家医保局人力资源社会保障部关于印发〈国家基本医疗保险、工伤保险和生育保险药品目录（2024年）〉的通知》（医保发〔2024〕33号）精神，根据《福建省医保药品单列门诊统筹支付管理办法（试行）》（闽医保规〔2024〕7号，以下简称《管理办法》）规定，我局制定了《单列门诊统筹支付的医保药品目录（2024年版）》，现予印发，自2025年4月15日起执行。具体信息请登录福建省医保局官网查看。附件：1.福建省单列门诊统筹支付医保药品目录（2024年版）.pdf2.继续保留“单列支付”管理的已转为常规目录原国谈药品.pdf3.不高于原国谈药品价格的同通用名药品.pdf相关文件请扫描上方二维码查看5、黄山市医保局：关于公布安徽省2024年度中成药集中带量采购中选结果的通知根据《安徽省2024年度中成药集中带量采购文件》（编号：AHYYCG-2024-07）要求，现公布安徽省2024年度中成药集中带量采购中选结果，详见附件。附件：1.安徽省2024年度中成药集中带量采购中选品种表.pdf2.安徽省2024年度中成药集中带量采购中选后供应品种清单.pdf相关文件请扫描上方二维码查看6、浙江省医保局：全省三级医疗机构谈判药品配备情况一览表(2025年第一季度)浙江省医保局发出《全省三级医疗机构谈判药品配备情况一览表(2025年第一季度)》（以下简称《一览表》），这是浙江省按季度定期发布的报告，是国谈药物在三级医疗机构的配备情况的权威数据。附件：全省三级医疗机构谈判药品配备情况一览表(2025年第一季度).pdf相关文件请扫描上方二维码查看7、上海阳光医药采购网：关于公布2025年2月药品挂网公开议价采购监管品种名单的通知根据《关于促进同通用名同厂牌药品省际间价格公平诚信、透明均衡的通知》（医保办函〔2023〕104号）、《药械重点监控监管工作规范》以及本市全面议价挂网相关文件的要求，本市进一步加强药品挂网公开议价采购的监管工作。现公布2025年2月挂网公开议价超“黄线”、未通过公允性评估、重点监控药品幅度靠前且有一定采购金额的品种，具体情况见附件。具体信息请登录上海阳光医药采购网官网查看。附件：1.新申请超“黄线”品种.pdf2.原在库超“黄线”品种.pdf3.未通过公允性品种.pdf4.重点监控品种.pdf相关文件请扫描上方二维码查看行业动态01药讯动态：重磅获批最近重磅获批卫材（Eisai）和渤健（Biogen）联合研发的药物Leqembi获得欧盟（EC）批准上市，用于治疗阿尔茨海默病早期阶段的轻度认知障碍。默沙东（MSD）申报的佳达修9[九价人乳头瘤病毒疫苗（酿酒酵母）]多项新适应证已获得NMPA上市批准，适用于16~26岁男性接种。Kowa Company（兴和制药）研发的新药佩玛贝特片获得NMPA批准上市。该药本次获批的适应症为治疗血脂异常。礼来公司（Eli Lilly and Company）申报的米吉珠单抗注射液（mirikizumab）以及其皮下注射剂型的新适应症上市申请获得CDE受理。本次该药申报上市的适应症为可能为治疗中重度活动性溃疡性结肠炎（UC）成人患者。诺诚健华申报的1类新药卓乐替尼片上市申请获得CDE受理，本次申报上市的适应症为用于治疗携带NTRK融合基因的晚期实体瘤成人和青少年（12周岁≤年龄<18周岁）。02药讯动态：重磅临床最近重磅临床翰森制药申报的1类新药HS-10529片获得CDE批准临床，拟开发治疗KRAS G12D突变的晚期实体瘤（胰腺癌、结直肠癌、非小细胞肺癌等）。 吉利德科学（Gilead Sciences）申报的seladelpar胶囊的临床试验申请获得CDE受理。这是一种新型选择性过氧化物酶体增殖物激活受体δ（PPARδ）激动剂。 康弘药业全资子公司康弘生物申报的1类新药注射用KH815获得CDE批准临床，拟开发治疗晚期实体瘤。 阿斯利康（AstraZeneca）申报的两款1类新药AZD6234注射液以及AZD9550注射液的临床试验申请获得CDE受理。AZD6234是一款多肽类药物，为每周一次皮下注射的长效胰淀素受体激动剂；AZD9550为每周一次的合成GLP-1/胰高血糖素（GCG）双受体激动剂。尧唐生物（YolTech Therapeutics）申报的1类新药YOLT-101注射液的临床试验申请获得CDE受理，这是尧唐生物在研的一款靶向PCSK9基因的体内碱基编辑药物。  03药企动态：市场动态4 月 15 日，勃林格殷格翰（BI）和 Cue Biopharma 宣布了一项战略研究合作和许可协议，以开发和商业化 Cue Biopharma 的 Cue -501 候选产品。根据协议条款，Cue Biopharma 的技术将被用于进一步研究和推进该候选分子的开发。作为回报，Cue Biopharma 将获得 1200 万美元的预付款，此外，Cue Biopharma 还有资格获得总计约 3.45 亿美元的研发和商业里程碑付款（包括两个临床前开发里程碑）以及净销售额的特许权使用费。4月15日，Cyprumed GmbH和默沙东宣布已签署非排他性许可和期权协议，使用Cyprumed的创新药物递送技术开发默沙东多肽的口服制剂。根据协议条款，默沙东获得了Cyprumed口服肽递送平台的非独家全球权利，靶点数量不详。该协议还授予默沙东独家许可Cyprumed技术用于单个靶点的选择权。4月16日，加利福尼亚州，专注于开发孤儿疾病变革性新疗法的生物技术公司Glycomine宣布完成1.15亿美元的C轮融资，将推进主要候选药物GLM101的2b期临床试验。此次融资由CTI Life Sciences Fund、abrdn管理的基金和Advent Life Sciences领投，现有投资者Novo Holdings、Sanofi Ventures、Abingworth、RiverVest Venture Partners、Sanderling Ventures、Chiesi Ventures、Remiges Ventures和Asahi Kasei Ventures继续投资。零售行业动态01河北省：全省药店，开始「双码绑定」根据国家医保局消息，河北在全省定点零售药店创新实现了“无码不结”，有效提升了追溯码信息采集率，推动“应采尽采、依码结算、依码支付”落地落实。河北省牢牢把握“不给定点增加额外工作负担”的原则，改造全省统一的定点业务办理子系统，增加药品追溯码信息维护功能，定点零售药店工作人员使用此功能建立起药品追溯码和医保编码的对照关系，并且对照关系实现“一家维护，全省通用”。结算时，通过扫描药品追溯码，系统自动关联出药品基础信息，减少手工录入环节，在提高结算效率的同时，也大大降低了手工录入错误率。具体信息请登录国家医保局官网查看。本周总结行业政策工业和信息化部办公厅关于发布首批中国消费名品名单的通知,推动医药品牌发展;国家卫健委召开2025年基层卫生健康综合试验区建设工作推进会，部署深化医改、推动资源整合和能力提升等重点工作；国家药监局发布通告，对18批次检出禁用原料的化妆品依法立案调查，并要求相关企业采取风险控制措施；上海阳光医药采购网公布2025年2月药品挂网公开议价采购监管品种名单，加强药品价格监管等。行业动态新药研发与获批领域亮点频现，多个新药在临床试验和上市审批方面取得突破性进展。卫材、默沙东、礼来等公司新药上市申请获得批准或受理，用于治疗阿尔茨海默病早期阶段的轻度认知障碍、血脂异常等疾病；翰森制药的HS-10529片、吉利德科学的seladelpar胶囊、康弘生物的注射用KH815、等新药获CDE批准或受理，涉及晚期实体瘤等领域；勃林格殷格翰与Cue Biopharma达成3.45亿美元合作；默沙东与Cyprumed签署非排他性许可协议；Glycomine完成1.15亿美元C轮融资。零售动态河北省全省药店实施“双码绑定”，通过药品追溯码与医保编码对照，提升结算效率和准确性。来源：由中国医药工业信息中心整理END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001