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Abstract Details

RAG-17, a Novel siRNA Therapy for SOD1-ALS: Safety and Preliminary Efficacy from a First-in-human Trial
Neuromuscular and Clinical Neurophysiology (EMG)
S5 - Updates on Amyotrophic Lateral Sclerosis (3:54 PM-4:06 PM)
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that typically results in survival of less than five years post-diagnosis. Superoxide Dismutase 1 (SOD1), the most frequently observed gene mutation in Asian ALS patients, has been targeted in past therapies with limited success. RAG-17 is a novel siRNA therapy targeting SOD1, conjugated to a smart chemistry aided delivery (SCAD) system for enhanced CNS delivery via intrathecal injection.

To evaluate the safety, pharmacokinetics, and preliminary efficacy of RAG-17 in SOD1-ALS patients.

This first-in-human, open-label, single-center, dose-escalation study (CREATION, NCT05903690) enrolled six SOD1-ALS patients to receive intrathecal injections of RAG-17 over a 240-day period.
Six participants received 6 to 7 doses, with dose escalations up to 150 mg, and one participant reaching 180 mg per dose. No dose-limiting toxicities (DLTs) or serious adverse events (SAEs) were reported. Adverse events were mild and included muscle tremors (2/6) and headaches (2/6). Plasma concentration of RAG-17 peaked at 6-12 hours post-administration and cleared within 48 hours. CSF SOD1 protein levels decreased by over 50% in five subjects. Plasma neurofilament light chain (NfL) levels also showed significant reductions. Notably, all subjects experienced an average decrease of 2.17 points in the ALS Functional Rating Scale-Revised (ALSFRS-R) score, equivalent to a 0.29-point decline per month. Forced vital capacity (FVC) remained stable in most patients, with two showing a significant increase from baseline.
The CREATION study demonstrates that RAG-17 is safe and exhibits potential efficacy in treating ALS patients. The results from this study highlight the therapeutic promise of RAG-17, offering new avenues for the management of ALS.
Authors/Disclosures
weiqi chen, MD
PRESENTER 		Dr. chen has received research support from Ractigen Therapeutics, Suzhou,China. The institution of Dr. chen has received research support from Beijing Nova Program .
Jinyi Ye The institution of Dr. ye has received research support from Ractigen Therapeutics, Suzhou, China.
Lingling Jiang, PhD Dr. Jiang has nothing to disclose.
ling wang, MS Miss wang has nothing to disclose.
Yuesong Pan, PhD Dr. pan has nothing to disclose.
Xuan Wang, PhD The institution of Dr. Wang has received research support from Ractigen Therapeutics, Suzhou,China.
Hui Qu, master of medicine Mr. Qu has received research support from Ractigen Therapeutics, Suzhou,China.
xiaoling liao, MD Dr. liao has received research support from Ractigen Therapeutics, Suzhou,China.
xuejiao zhou, Bachelor of Nursing The institution of Miss zhou has received research support from Ractigen Therapeutics, Suzhou,China.
Shawn Zhang, MD Ms. Zhang has nothing to disclose.
Moorim Kang, PhD Dr. Kang has nothing to disclose.
Long-Cheng Li, MD Dr. Li has stock in Ractigen Therapeutics. Dr. Li has received intellectual property interests from a discovery or technology relating to health care.
Yilong Wang, MD The institution of Dr. Wang has received research support from Ractigen Therapeutics, Suzhou, China. The institution of Dr. Wang has received research support from the National Natural Science Foundation of China. The institution of Dr. Wang has received research support from Capital's Funds for Health Improvement and Research. The institution of Dr. Wang has received research support from National Key R&D Program of China. The institution of Dr. Wang has received research support from Beijing Laboratory of Oral Health. The institution of Dr. Wang has received research support from Beijing Municipal Science & Technology Commission. The institution of Dr. Wang has received research support from Noncommunicable Chronic Diseases-National Science and Technology Major Project .