Ractigen Therapeutics Announces Promising Phase I Data for RAG-01, a First-in-Class saRNA Therapy Demonstrating 66.7% Complete Response Rate in BCG-Unresponsive NMIBC

Mar 25, 2025 10:25 CST Updated 10:25

Ractigen

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On March 24, Ractigen Therapeutics announced at the latest breakthrough session of the 40th Annual Meeting of the European Association of Urology (EAU 2025) held in Madrid, Spain, that it had released itsRAG-01 for the Treatment of Non-Muscle-Invasive Bladder Cancer (NMIBC)Positive preliminary data from Phase 1 clinical trials. The data shows,In patients who failed BCG treatment, the complete response (CR) rate of carcinoma in situ (CIS) patients in the two lowest dose groups reached 66.7%., and its safety performance is excellent.

RAG-01 is an innovative saRNA (small activating RNA) therapy designed to upregulatep21Expression of tumor suppressor genes.p21Genes play a key regulatory role in the cell cycle process, but traditional therapies struggle to effectively target them. Leveraging Ractigen Therapeutics' proprietary LiCO delivery technology,RAG-01, administered via intravesical instillation, offers a novel therapeutic option for NMIBC patients who have failed BCG treatment.Given its potential in areas of unmet clinical needs, RAG-01 has been granted Fast Track designation by the U.S. FDA and has also received IND approval in the United States.

The ongoing Phase 1 clinical trial is an open-label, multi-center study using a standard “3+3” dose escalation design. The primary objectives are 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 9 patients have participated in the trial, receiving treatments at three dose levels: 30mg, 100mg, and 300mg. The treatment regimen includes a 6-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 include:

Better Safety:No dose-limiting toxicity (DLT) was observed in any of the dose groups.88.9% (8/9) of patients reported treatment-related adverse events (AEs), but all adverse events were grade 2 or lower in severity.The most common adverse reactions (incidence rate of 11.1% each) include urinary urgency, urinary frequency, and urinary tract infection.
Precise Drug Delivery and Target Activation:Pharmacokinetic analysis showed that RAG-01 had very low exposure in systemic blood, confirming the effectiveness of intravesical administration and the LiCO delivery system.The concentration of RAG-01 in urine increased in a dose-dependent manner, with a range of 83.3 to 1820 µg/ml two hours after administration.Meanwhile, the proportion of p21-positive cells in the bladder urothelium also increased in a dose-dependent manner, confirming the drug's target engagement.
Significant Early Efficacy:In patients with carcinoma in situ, the complete response rate in the lowest two dose groups (30mg and 100mg) reached 66.7% (2/3).Moreover, 66.7% (2/3) of patients with papillary tumors showed no recurrence of the disease at the 3-month follow-up.These early efficacy data fully demonstrate that even at lower doses, RAG-01 still exhibits remarkably 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," said Dr. Longcheng Li, CEO of Ractigen Therapeutics. "Even in the lowest dose group, we observed a significant complete response rate, while the drug demonstrated excellent safety profiles. This not only confirms the breakthrough innovation 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."

Dr. Paul Anderson from the Royal Melbourne Hospital in Australia stated, "The significant complete response rate observed in these early cohorts is very encouraging, especially for BCG-unresponsive NMIBC patients who currently have limited treatment options. These results lay a solid foundation for further exploration of RAG-01's potential in this challenging disease."

According to the press release, Ractigen Therapeutics plans to continue advancing the dose escalation and dose expansion of RAG-01 to further evaluate its safety and efficacy and determine the optimal dosage. The company is committed to accelerating the clinical development process of RAG-01, providing a breakthrough new treatment option for NMIBC patients.

References:

[1] Ractigen's RAG-01 Phase I Clinical Trial for Non-Muscle-Invasive Bladder Cancer Shows Promising Early Complete Response Rate at EAU 2025. Retrieved Mar 24, 2025, from https://mp.weixin.qq.com/s/z3Acz47XQqMP-CAwKlzTeQ

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