中美瑞康RAG-01非肌层浸润性膀胱癌I期临床试验早期数据亮相EAU 2025，展现积极完全缓解率

RAG-01作为一种创新性的saRNA疗法，旨在上调p21肿瘤抑制基因的表达。p21基因在细胞周期进程中起关键调控作用，然而传统疗法却难以对其实现有效靶向。凭借中美瑞康自主研发的 LiCO™递送技术，RAG-01采用膀胱灌注的给药方式，为BCG治疗失败的 NMIBC患者提供了一种全新的治疗方案。鉴于其在尚未满足的临床需求领域所展现出的潜力，RAG-01已成功获得美国 FDA 的快速通道资格认定（Fast Track Designation）和IND许可。

正在进行的I期临床试验（NCT06351904）是一项开放标签、多中心的研究，采用标准的“3+3”剂量递增设计，主要目标是评估RAG-01的安全性、耐受性、药代动力学（PK）和药效动力学（PD），并探索初步疗效。截至2024年12月15日，共有9名患者参与试验，分别接受了30 mg、100 mg和300 mg三个剂量水平的治疗。治疗方案包括为期6周的每周一次的诱导治疗，以及在第12、24、36、48和72周的维持治疗。

“这些早期临床数据令人鼓舞，有力地验证了我们saRNA平台在攻克肿瘤治疗难题中的独特价值，”中美瑞康首席执行官李龙承博士表示。“即使在最低剂量组，我们就观察到了显著的完全缓解率，同时药物展现出优异的安全性特征。这不仅证实了RAG-01背后的RNA激活技术具有突破性创新价值，也表明它很可能成为BCG难治性非肌层浸润性膀胱癌患者的重要治疗选择。”

澳大利亚皇家墨尔本医院的Paul Anderson博士表示：“在这些早期队列中观察到的显著完全缓解率非常鼓舞人心，特别是对于目前治疗选择有限的BCG无应答NMIBC患者而言。这些结果为进一步探索RAG-01在这一挑战性疾病中的潜力奠定了坚实基础。”

下一步开发计划

非肌层浸润性膀胱癌（NMIBC）是一种常见的恶性肿瘤，病变局限于膀胱内壁。标准一线治疗是经尿道膀胱肿瘤切除术（TURBT），随后进行膀胱内BCG免疫治疗。然而，相当比例的患者会出现复发或对BCG治疗无反应，因此亟需开发新型有效的治疗方法。

RNA激活（RNAa）是一种经过临床验证的技术平台，由李龙承博士及其团队首创。RNAa通过小激活RNA（saRNA）靶向特定基因调控区域，选择性激活基因表达，进而恢复治疗性蛋白的产生。这一创新技术在多种疾病领域具有广泛的治疗潜力，特别是在遗传性疾病和癌症等传统治疗方法效果不佳的领域。

中美瑞康（Ractigen Therapeutics）是一家临床阶段的生物制药公司，致力于开发突破性小核酸药物与疾病治疗方法。中美瑞康是全球少数同时掌握有肝内与肝外递送的小核酸药企之一，开发出了具有独立自主知识产权的SCAD™、LiCO™及GLORY™等多个具有国际领先水平的小核酸药物递送平台技术。基于RNA激活技术和自主开发的Smart-TTC saRNA药物开发平台，公司建立了具有高度差异化的小核酸药物管线，适应症涵盖神经退行性疾病、神经肌肉疾病、肿瘤、代谢与血液系统疾病等，为诸多疾病领域中无法成药的靶点、无法治愈的疾病提供创新型治疗方案。详情请访问官网www.ractigen.com。

NANTONG, China, and MELBOURNE, Australia, March 24, 2025 – Ractigen Therapeutics, a clinical-stage biopharmaceutical company pioneering small activating RNA (saRNA) therapeutics, today announced the presentation of positive preliminary data from its ongoing Phase I clinical trial of RAG-01, a first-in-class saRNA therapy for the treatment of non-muscle invasive bladder cancer (NMIBC). The data were presented in a late breaking session by Dr. Paul Anderson of The Royal Melbourne Hospital, Australia, at the 40th Annual Congress of the European Association of Urology (EAU 2025) in Madrid, Spain. The results demonstrate a remarkable 66.7% complete response (CR) rate in carcinoma in situ (CIS) patients within the two lowest dose cohorts, along with a favorable safety profile, in patients who have failed Bacillus Calmette-Guérin (BCG) therapy.

RAG-01 is an innovative saRNA therapy designed to upregulate the p21 tumor suppressor gene, a key regulator of cell cycle progression that has been challenging to target with traditional therapies. Administered into the bladder via intravesical instillation using Ractigen’s proprietary LiCO™ delivery technology, RAG-01 offers a novel approach to treating NMIBC, particularly in patients unresponsive to BCG therapy. The therapy has received FDA Fast Track Designation, reflecting its potential to address a significant unmet medical need in this patient population.

About the Phase I Study

The ongoing Phase I trial (NCT06351904) is an open-label, multi-center study employing a standard 3+3 dose-escalation design. The primary objectives are to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RAG-01. The study also assesses preliminary efficacy. As of the data cutoff date (December 15, 2024), nine patients had been enrolled across three dose cohorts: 30 mg, 100 mg, and 300 mg. The treatment regimen consists of a 6-week induction course of weekly instillations, followed by maintenance instillations at weeks 12, 24, 36, 48, and 72.

Key Findings Presented at EAU 2025

• Excellent Safety Profile: No dose-limiting toxicities (DLTs) were observed at any of the dose levels evaluated. Treatment-related adverse events (AEs) were reported in 88.9% (8/9) of patients, but all were Grade 2 or lower in severity. The most frequently reported AEs (each occurring in 11.1% of patients) were urinary urgency, increased urinary frequency, and urinary tract infection.

• Targeted Drug Delivery and Activity:  PK analysis revealed minimal systemic exposure of RAG-01, confirming the effectiveness of the intravesical administration and LiCO™ technology. Dose-dependent increases in RAG-01 urine concentrations were observed, ranging from 83.3 to 1,820µg/ml at 2 hours post-instillation. Importantly, a dose-dependent increase in p21-positive urothelial cells was observed, confirming successful target engagement and on-mechanism activity of RAG-01.

• Remarkable Early Efficacy: In patients with carcinoma in situ (CIS), the complete response (CR) rate was 66.7% (2/3 patients). Furthermore, 66.7% (2/3) of patients with papillary tumors remained disease-free at the 3-month assessment. These promising efficacy signals were observed in the two lowest dose cohorts (30mg and 100mg), highlighting the potential of RAG-01 even at early stages of clinical development.

“These preliminary findings are incredibly exciting and validate the potential of our saRNA platform to address significant unmet needs in oncology,” said Dr. Long-Cheng Li, Founder and CEO of Ractigen Therapeutics, “Achieving such a high complete response rate in the lowest dose cohorts, with a favorable safety profile, is a testament to the innovative science behind RAG-01 and its potential to become a transformative therapy for patients with BCG-unresponsive NMIBC.”

Dr. Paul Anderson, the investigator of The Royal Melbourne Hospital, stated, “The striking CR rates observed in these early cohorts are highly encouraging, particularly for BCG-unresponsive NMIBC patients who currently have limited treatment options. These results pave the way for further exploration of RAG-01’s capabilities in this challenging disease.”

Next Steps

Ractigen Therapeutics plans to advance the RAG-01 clinical program by continuing dose escalation and initiating dose-expansion cohorts to further evaluate the therapy's safety, efficacy and determine the optimal dose. The company is committed to rapidly progressing RAG-01 through clinical development, with the goal of providing a groundbreaking new treatment option for patients with NMIBC.

About NMIBC

Non-muscle invasive bladder cancer (NMIBC) is a common malignancy confined to the lining of the bladder. The standard first-line treatment is transurethral resection of the bladder tumor (TURBT) followed by intravesical BCG immunotherapy. However, a significant proportion of patients experience recurrence or become unresponsive to BCG, highlighting the need for new and effective treatment options.

About RNAa

RNAa is a clinically validated platform technology, pioneered by Dr. Long-Cheng Li and his team, that harnesses the power of small activating RNAs (saRNAs). saRNAs are double-stranded RNA oligonucleotides that target specific gene regulatory regions to selectively activate gene expression, restoring the production of therapeutic proteins. This innovative technology has broad therapeutic potential across a range of diseases, particularly where traditional therapeutic approaches have proven insufficient, including genetic disorders and cancers.

About Ractigen Therapeutics

Ractigen Therapeutics is a clinical-stage biopharmaceutical company dedicated to advancing next-generation RNA-based therapies. Leveraging its groundbreaking, clinically validated RNA activation (RNAa) technology, Ractigen utilizes small activating RNAs (saRNAs) to selectively upregulate the expression of therapeutically relevant genes. Supported by proprietary drug delivery technologies—including SCAD™, LiCO™ and GLORY™, Ractigen is rapidly building an innovative pipeline targeting significant unmet medical needs across oncology, genetic disorders, and beyond. Driven by a commitment to scientific excellence and patient-focused innovation, Ractigen aims to transform patient outcomes and improve lives worldwide through the transformative power of RNA therapeutics. 

For more information, please visit our website: www.ractigen.com.