On March 24, 2025 Ractigen Therapeutics, a clinical-stage biopharmaceutical company pioneering small activating RNA (saRNA) therapeutics, reported 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) (Press release, Ractigen, MAR 24, 2025, View Source [SID1234651379]). 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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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 1,820 µg/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 (30 mg and 100 mg), 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, 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.