Ractigen Therapeutics Highlights Promising Phase I Data of RAG-01 saRNA Therapy for BCG-Unresponsive NMIBC in IPO Filing
Ractigen
Innovative Drug R&D Developer
On March 24, 2025, Ractigen Therapeutics, a clinical-stage biopharmaceutical company focused on small activating RNA (saRNA) therapies, announced the presentation of positive preliminary data from its Phase I clinical trial of RAG-01 for the treatment of non-muscle invasive bladder cancer (NMIBC) at the Late-Breaking Abstract Session of the 40th Annual European Association of Urology Congress (EAU 2025) held in Madrid, Spain. Dr. Paul Anderson from the Royal Melbourne Hospital in Australia presented the findings. The data showed that among patients who had failed Bacillus Calmette-Guérin (BCG) therapy, the complete response rate (CR) for carcinoma in situ (CIS) patients in the two lowest dose groups reached 66.7%, with an excellent safety profile.
RAG-01, as an innovative saRNA therapy, aims to upregulate the expression of the p21 tumor suppressor gene. The p21 gene plays a crucial regulatory role in cell cycle progression; however, traditional therapies struggle to effectively target it. Utilizing Ractigen Therapeutics' proprietary LiCO™ delivery technology, RAG-01 is administered via intravesical instillation, offering a novel treatment option for NMIBC patients who have failed BCG therapy. Given its demonstrated potential in addressing unmet clinical needs, RAG-01 has successfully received Fast Track Designation and IND approval from the U.S. FDA.
Phase I Clinical Trial of RAG-01
The ongoing Phase I clinical trial (NCT06351904) is an open-label, multi-center study utilizing a standard “3+3” dose-escalation design. Its primary objective is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RAG-01, while exploring preliminary efficacy. As of December 15, 2024, a total of nine patients have participated in the trial, receiving treatment at three dose levels: 30 mg, 100 mg, and 300 mg. The treatment regimen includes a six-week induction phase with once-weekly dosing, followed by maintenance therapy at weeks 12, 24, 36, 48, and 72.
Key Research Results Presented at EAU 2025
Excellent Safety:No dose-limiting toxicity (DLT) was observed in any of the dose groups. Treatment-related adverse events (AEs) were reported in 88.9% (8/9) of patients, but all adverse events were grade 2 or lower in severity. The most common adverse reactions (each with an incidence rate of 11.1%) included urgency of urination, urinary frequency, and urinary tract infection.
Precision Drug Delivery and Target Activation:Pharmacokinetic analysis showed that the systemic exposure of RAG-01 in the blood was extremely low, confirming the effectiveness of intravesical administration and the LiCO™ delivery system. Urinary concentrations of RAG-01 increased in a dose-dependent manner, ranging from 83.3 to 1820 µg/ml at 2 hours post-administration. Meanwhile, the proportion of p21-positive cells in the bladder urothelium also increased in a dose-dependent manner, confirming target engagement of the drug.
Significant Early Efficacy:In patients with carcinoma in situ, the complete response rate in the two lowest dose groups (30mg and 100mg) reached 66.7% (2/3). Additionally, 66.7% (2/3) of patients with papillary tumors showed no disease recurrence at the 3-month follow-up. These early efficacy data strongly indicate that even at lower doses, RAG-01 still demonstrated highly significant therapeutic effects.
"These early clinical data are encouraging and strongly validate the unique value of our saRNA platform in addressing the challenges of cancer treatment."Dr. Longcheng Li, CEO of Ractigen"We observed a significant complete response rate even in the lowest dose group, while the drug demonstrated excellent safety characteristics. This not only confirms the breakthrough innovative value of the RNA activation technology behind RAG-01 but also suggests that it is likely to become an important treatment option for patients with BCG-refractory non-muscle invasive bladder cancer."
The Royal Melbourne Hospital, AustraliaDr. Paul AndersonSaid: "The significant complete response rate observed in these early cohorts is very encouraging, especially for patients with BCG-unresponsive NMIBC who currently have limited treatment options. These results lay a solid foundation for further exploration of the potential of RAG-01 in this challenging disease."
Next Step Development Plan
Ractigen plans to continue advancing the dose escalation and expansion of RAG-01 to further evaluate its safety and efficacy and determine the optimal dose. The company is committed to accelerating the clinical development process of RAG-01, providing a breakthrough new treatment option for NMIBC patients.
About Non-Muscle-Invasive Bladder Cancer
Non-Muscle-Invasive Bladder Cancer (NMIBC) is a common malignant tumor, with lesions confined to the inner wall of the bladder. The standard first-line treatment is Transurethral Resection of Bladder Tumor (TURBT), followed by intravesical BCG immunotherapy. However, a significant proportion of patients experience recurrence or show no response to BCG treatment, highlighting an urgent need for the development of novel and effective therapeutic approaches.
About RNA Activation
RNA Activation (RNAa) is a clinically validated technology platform pioneered by Dr. Li Longcheng and his team. RNAa selectively activates gene expression by targeting specific gene regulatory regions with small activating RNAs (saRNAs), thereby restoring the production of therapeutic proteins. This innovative technology holds broad therapeutic potential across various disease areas, particularly in fields such as genetic disorders and cancers where traditional treatments have shown limited efficacy.
About Ractigen
Ractigen Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing breakthrough small nucleic acid drugs and disease treatment methods. Ractigen Therapeutics is one of the few global small nucleic acid drug companies that simultaneously masters both intrahepatic and extrahepatic delivery technologies, having developed multiple internationally leading small nucleic acid drug delivery platform technologies with independent intellectual property rights, including SCAD™, LiCO™, and GLORY™. Based on RNA activation technology and its self-developed Smart-TTC saRNA drug development platform, the company has established a highly differentiated small nucleic acid drug pipeline with indications covering neurodegenerative diseases, neuromuscular diseases, cancer, metabolic diseases, and hematological disorders, providing innovative therapeutic solutions for undruggable targets and currently incurable diseases across various disease areas.
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