中美瑞康宣布《自然·医学》发表其与天坛医院合作完成的里程碑式论文，详述RAG-17治疗SOD1-ALS突破性临床前疗效及积极的首次人体临床数据 。
- 经同行评审的重磅论文详述了RAG-17从“实验台到病床”的强劲转化表现，全面验证了中美瑞康专有SCAD™递送平台在中枢神经系统（CNS）靶向RNAi疗法中的巨大潜力 -
- 首次人体临床研究（FIH）达到主要安全性终点，未发生严重不良事件（SAE）；脑脊液（CSF）中SOD1蛋白平均降低达69%，血浆NfL平均降低62% -
- 临床前模型显示，即使在疾病晚期给药，RAG-17仍能带来前所未有的生存期显著延长及运动功能挽救 -
中国南通，2026年7月15日——致力于开发下一代RNA靶向药物的临床阶段生物制药公司中美瑞康（Ractigen Therapeutics）今日宣布，其在国际顶级医学期刊《自然·医学》（Nature Medicine）上发表了一篇经过同行评审的重量级长篇论文。该论文详细披露了RAG-17（一种旨在治疗由超氧化物歧化酶1（SOD1）基因突变引起的肌萎缩侧索硬化症的在研小干扰RNA（siRNA）疗法）的临床前药理学机制、非人灵长类动物（NHP）靶点结合数据，以及令人振奋的首次人体（FIH）I期临床结果。
图片来源 公众号：中美瑞康
RAG-17采用了中美瑞康拥有完全自主知识产权的智能化学辅助递送（SCAD™）技术。该技术将siRNA双链与特殊设计的辅助寡核苷酸（ACO）进行偶联，突破了递送壁垒，使药物在单次鞘内（IT）注射后即可在中枢神经系统（CNS）实现广泛分布，并产生极其持久的致病基因沉默效果。
“SOD1-ALS是一种极具破坏性且进展迅速的毁灭性疾病。尽管近年来的治疗进展为患者带来了一线曙光，但临床上仍然迫切需要药效更强、作用更持久且患者依从性更好的治疗方案，”该论文通讯作者、首都医科大学附属北京天坛医院神经病学中心首席科学家王伊龙教授评论道，“我们在这些受试患者身上观察到了令人信服的生物标志物积极响应和良好的安全性，再结合晚期动物模型中表现出的史无前例的生存获益，这些综合证据强烈预示着RAG-17有潜力成为同类最佳（best-in-class）的疾病修饰疗法。”
“能够将RAG-17详实且高质量的临床前及临床数据集发表在《自然·医学》这样享有盛誉的期刊上，是对我们科学理念和SCAD™递送平台的深度背书，”中美瑞康创始人兼首席执行官李龙承博士表示，“将siRNA安全、精准地递送至中枢神经系统，实现深度且持久的靶点结合，在严苛的临床前模型中显著逆转疾病进程——并将这些优异的数据成功在患者身上得到转化，这无疑是寡核苷酸疗法领域的一个重大里程碑。患者脑脊液中SOD1致病蛋白以及神经丝轻链蛋白（NfL）的大幅下降令我们深受鼓舞。我们将全力推进RAG-17的后续临床开发，争取早日为SOD1-ALS患者群体带来一种强效且能大幅减少给药频率的颠覆性治疗选择。”
积极的首次人体（FIH）临床数据
这项开放标签、剂量递增的研究者发起的临床试验（IIT），全面评估了6名SOD1-ALS患者接受多次鞘内注射RAG-17的安全性、耐受性、药代动力学及药效学特征。
极佳的安全性特征：RAG-17成功达到主要安全性终点。药物整体耐受性良好，截至数据截止日，未报告任何严重不良事件（SAE），患者也均未需要使用有创机械通气。治疗出现的不良事件（TEAE）均为轻度至中度，呈一过性且临床完全可控。
生物标志物的大幅降低：RAG-17实现了关键生物标志物持续且显著的下降。在队列1中，患者脑脊液（CSF）中的SOD1蛋白在第240天时平均下降了69%；同时，作为神经轴突损伤关键标志物的血浆NfL平均下降了62%，部分患者个体的最大降幅甚至超过基线水平的85%。
临床疾病稳定迹象：探索性的初步临床数据显示，部分患者的疾病进程趋于稳定或功能衰退显著放缓。值得注意的是，在整个研究随访期间，部分受试者的呼吸功能（用力肺活量（FVC）占预计值的百分比）得到了维持甚至改善。
突破性的临床前疗效
该论文还系统性地展示了RAG-17在多个物种中详尽的体内（in vivo）药效学表现：
啮齿类动物模型的晚期挽救（Late-Stage Rescue）：在疾病快速且致命进展的SOD1-G93A小鼠模型中，即使在症状明显发作后的晚期阶段（出生后第126天和第151天）进行给药，RAG-17依然展现出惊人的疾病修饰疗效。与对照组相比，晚期治疗将小鼠的生存期大幅延长了75.8%（128.5天），并成功恢复了运动功能，遏制了体重下降。在疾病大鼠模型中，RAG-17更是从根本上推迟了疾病的发病时间，并显著保护了脊髓运动神经元免受损伤。
非人灵长类动物（NHP）的持久靶点敲低：在食蟹猴中，单次鞘内注射RAG-17可使腰髓中的SOD1 mRNA水平下降高达91%，且这种深度基因沉默效果在给药后维持长达72天。这强有力地表明，相较于目前的现有疗法，RAG-17在临床应用上有望大幅延长患者的给药间隔，减轻治疗负担。
该论文题为“Oligonucleotide–siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial”，现已在《自然·医学》（Nature Medicine）官方网站在线发表。
（DOI: doi.org/10.1038/s41591-026-04491-7）
图片来源 公众号：中美瑞康
关于RAG-17
RAG-17是一款处于临床开发阶段的新型siRNA疗法，特异性靶向SOD1 mRNA转录本。得益于中美瑞康自主研发的SCAD™（智能化学辅助递送）平台，RAG-17旨在极其强效且持久地沉默中枢神经系统内有毒性的突变型SOD1蛋白的表达，从而显著降低患者进行鞘内注射给药的频率。
关于中美瑞康
中美瑞康（Ractigen Therapeutics）是一家临床阶段的生物制药公司，专注于开发下一代RNA疗法，以临床验证的RNA激活（RNAa）技术为基础，致力于推进基于小激活RNA（saRNA）的创新治疗方案。依托SCAD™、LiCO™和GLORY™等自主研发的小核酸药物递送平台，公司正在推进覆盖肿瘤、神经系统疾病及遗传疾病等多个领域的候选管线，持续满足未竟的临床需求。公司多功能技术平台亦支持针对中枢神经系统等危及生命疾病快速开发RNA解决方案，包括siRNA药物。中美瑞康始终秉持科学卓越与以患者为中心的创新理念，致力于以RNA疗法推动医疗进步。更多信息，请访问www.ractigen.com。
Ractigen Therapeutics Announces Landmark Publication in Nature Medicine Highlighting Unprecedented Preclinical Efficacy and Positive First-in-Human Clinical Data for RAG-17 in SOD1-ALS
- Peer-reviewed publication details RAG-17’s robust translation from "bench to bedside," validating the proprietary SCAD™ delivery platform for CNS-targeted RNAi therapies -
- First-in-Human trial met primary safety endpoints with no Serious Adverse Events (SAEs); demonstrated mean reductions of up to 69% in CSF SOD1 protein and 62% in plasma NfL -
- Preclinical models showed RAG-17 yielded unprecedented survival extension and functional rescue, even when administered at an advanced disease stage -
NANTONG, China, July 15, 2026 — Ractigen Therapeutics, a clinical-stage biopharmaceutical company pioneering the development of next-generation RNA-based therapeutics, today announced the publication of a comprehensive peer-reviewed paper in Nature Medicine. The manuscript details the preclinical pharmacology, non-human primate (NHP) target engagement, and positive First-in-Human (FIH) Phase 1 clinical data for RAG-17, an investigational small interfering RNA (siRNA) therapy for the treatment of amyotrophic lateral sclerosis (ALS) driven by mutations in the superoxide dismutase 1 (SOD1) gene.
RAG-17 utilizes Ractigen’s proprietary Smart Chemistry-Aided Delivery (SCAD™) technology, which conjugates the siRNA duplex to a specialized accessory oligonucleotide (ACO). This allows for broad distribution throughout the central nervous system (CNS) and highly durable gene silencing following intrathecal (IT) injection.
"SOD1-ALS is a devastating and rapidly progressive disease. While recent therapeutic advances have provided hope, there remains a critical need for therapies with improved potency, durability, and patient convenience," stated Dr. Yilong Wang, corresponding author and Principal Investigator from the Department of Neurology at Beijing Tiantan Hospital. "The compelling biomarker responses and safety profile we have observed in these patients, combined with the unprecedented survival benefit seen in advanced-stage animal models, suggest that RAG-17 has the potential to be a best-in-class disease-modifying therapy."
"The publication of our extensive RAG-17 dataset in a journal as prestigious as Nature Medicine is a profound validation of our scientific approach and the SCAD platform," said Dr. Long-Cheng Li, Founder and CEO of Ractigen Therapeutics. "The ability to safely deliver an siRNA directly to the CNS, achieve deep and durable target engagement, and dramatically alter the disease course in rigorous preclinical models—and now, to see these results successfully translate into humans—marks a major milestone for oligonucleotide therapeutics. We are incredibly encouraged by the substantial reductions in both disease-driving SOD1 protein and neurofilament light chain (NfL) in our patients, and we look forward to advancing RAG-17 to bring a highly potent, less frequently dosed treatment option to the SOD1-ALS community."
Positive First-in-Human Clinical Data
The open-label, dose-escalation investigator-initiated trial evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple intrathecal RAG-17 doses in six patients with SOD1-ALS.
Favorable Safety Profile: RAG-17 met its primary safety endpoint. It was well-tolerated, with no serious adverse events (SAEs) and no requirement for invasive mechanical ventilation up to the data cutoff. Treatment-emergent adverse events (TEAEs) were mild to moderate, transient, and manageable.
Robust Biomarker Reductions: RAG-17 achieved substantial, progressive reductions in key biomarkers. In Cohort 1, mean cerebrospinal fluid (CSF) SOD1 protein decreased by 69% at Day 240, while plasma NfL—a critical marker of neuroaxonal damage—decreased by a mean of 62%, with individual nadirs reaching up to 85% below baseline.
Clinical Stabilization: Preliminary exploratory data indicated disease stabilization or decelerated functional decline in certain patients. Notably, respiratory function (percent predicted FVC) was maintained or improved in specific participants over the study duration.
Unprecedented Preclinical Efficacy
The publication also highlighted extensive in vivo profiling of RAG-17 across multiple species:
Late-Stage Rescue in Rodents: In aggressively progressing SOD1G93A mouse models, RAG-17 demonstrated remarkable efficacy even when administered significantly after symptom onset (postnatal days 126 and 151). Late-stage treatment extended survival by up to 75.8% (128.5 days) compared to controls, alongside restored motor function and preserved body weight. In rat models, RAG-17 fundamentally delayed disease onset and preserved spinal motor neurons.
Durable Knockdown in NHPs: In cynomolgus monkeys, intrathecal RAG-17 achieved up to 91% reduction of SOD1 mRNA in the lumbar spinal cord, an effect that persisted for up to 72 days post-dose, suggesting the potential for significantly extended dosing intervals in the clinic compared to current therapies.
The full manuscript, titled "Oligonucleotide–siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial," is now available online in Nature Medicine.
(DOI: doi.org/10.1038/s41591-026-04491-7)
About RAG-17
RAG-17 is a novel, Phase II siRNA therapeutic targeting the SOD1 mRNA transcript. By leveraging the SCAD™ (Smart Chemistry-Aided Delivery) platform, RAG-17 is designed to silence the production of toxic mutant SOD1 protein in the CNS with high potency and extended durability, reducing the need for frequent intrathecal injections.
About Ractigen Therapeutics
Ractigen Therapeutics is a clinical-stage biopharmaceutical company innovating next-generation RNA therapeutics, with a primary focus on small activating RNAs (saRNAs) developed through its clinically validated RNA activation (RNAa) technology. Leveraging proprietary delivery platforms such as SCAD™, LiCO™, and GLORY™, Ractigen is advancing a robust pipeline addressing unmet medical needs in oncology, neurological diseases, and genetic disorders. Its versatile technologies also enable the rapid development of RNA-based solutions, including siRNAs, where applicable, to target life-threatening, fast-progressing conditions such as those in the CNS. Committed to scientific excellence and patient-centered innovation, Ractigen strives to transform healthcare through the power of RNA therapeutics. For more information, visit www.ractigen.com.
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2026-07-22
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