— Peer-reviewed publication details RAG-17’s robust translation from “bench to bedside,” validating the proprietary SCAD™ delivery platform for CNS-targeted RNAi therapies —
— First-in-Human trial met primary safety endpoints with no Serious Adverse Events (SAEs); demonstrated mean reductions of up to 69% in CSF SOD1 protein and 62% in plasma NfL —
— Preclinical models showed RAG-17 yielded unprecedented survival extension and functional rescue, even when administered at an advanced disease stage —
NANTONG, China, July 15, 2026 /PRNewswire/ — Ractigen Therapeutics, a clinical-stage biopharmaceutical company pioneering the development of next-generation RNA-based therapeutics, today announced the publication of a comprehensive peer-reviewed paper in Nature Medicine. The manuscript details the preclinical pharmacology, non-human primate (NHP) target engagement, and positive First-in-Human (FIH) Phase 1 clinical data for RAG-17, an investigational small interfering RNA (siRNA) therapy for the treatment of amyotrophic lateral sclerosis (ALS) driven by mutations in the superoxide dismutase 1 (SOD1) gene.
RAG-17 utilizes Ractigen’s proprietary Smart Chemistry-Aided Delivery (SCAD™) technology, which conjugates the siRNA duplex to a specialized accessory oligonucleotide (ACO). This allows for broad distribution throughout the central nervous system (CNS) and highly durable gene silencing following intrathecal (IT) injection.
“SOD1-ALS is a devastating and rapidly progressive disease. While recent therapeutic advances have provided hope, there remains a critical need for therapies with improved potency, durability, and patient convenience,” stated Dr. Yilong Wang, corresponding author and Principal Investigator from the Department of Neurology at Beijing Tiantan Hospital. “The compelling biomarker responses and safety profile we have observed in these patients, combined with the unprecedented survival benefit seen in advanced-stage animal models, suggest that RAG-17 has the potential to be a best-in-class disease-modifying therapy.”
“The publication of our extensive RAG-17 dataset in a journal as prestigious as Nature Medicine is a profound validation of our scientific approach and the SCAD platform,” said Dr. Long-Cheng Li, Founder and CEO of Ractigen Therapeutics. “The ability to safely deliver an siRNA directly to the CNS, achieve deep and durable target engagement, and dramatically alter the disease course in rigorous preclinical models—and now, to see these results successfully translate into humans—marks a major milestone for oligonucleotide therapeutics. We are incredibly encouraged by the substantial reductions in both disease-driving SOD1 protein and neurofilament light chain (NfL) in our patients, and we look forward to advancing RAG-17 to bring a highly potent, less frequently dosed treatment option to the SOD1-ALS community.”
Positive First-in-Human Clinical Data
The open-label, dose-escalation investigator-initiated trial evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple intrathecal RAG-17 doses in six patients with SOD1-ALS.
- Favorable Safety Profile: RAG-17 met its primary safety endpoint. It was well-tolerated, with no serious adverse events (SAEs) and no requirement for invasive mechanical ventilation up to the data cutoff. Treatment-emergent adverse events (TEAEs) were mild to moderate, transient, and manageable.
- Robust Biomarker Reductions: RAG-17 achieved substantial, progressive reductions in key biomarkers. In Cohort 1, mean cerebrospinal fluid (CSF) SOD1 protein decreased by 69% at Day 240, while plasma NfL—a critical marker of neuroaxonal damage—decreased by a mean of 62%, with individual nadirs reaching up to 85% below baseline.
- Clinical Stabilization: Preliminary exploratory data indicated disease stabilization or decelerated functional decline in certain patients. Notably, respiratory function (percent predicted FVC) was maintained or improved in specific participants over the study duration.
Unprecedented Preclinical Efficacy
The publication also highlighted extensive in vivo profiling of RAG-17 across multiple species:
- Late-Stage Rescue in Rodents: In aggressively progressing SOD1G93A mouse models, RAG-17 demonstrated remarkable efficacy even when administered significantly after symptom onset (postnatal days 126 and 151). Late-stage treatment extended survival by up to 75.8% (128.5 days) compared to controls, alongside restored motor function and preserved body weight. In rat models, RAG-17 fundamentally delayed disease onset and preserved spinal motor neurons.
- Durable Knockdown in NHPs: In cynomolgus monkeys, intrathecal RAG-17 achieved up to 91% reduction of SOD1 mRNA in the lumbar spinal cord, an effect that persisted for up to 72 days post-dose, suggesting the potential for significantly extended dosing intervals in the clinic compared to current therapies.
The full manuscript, titled “Oligonucleotide–siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial“, is now available online in Nature Medicine. (DOI: https://doi.org/10.1038/s41591-026-04491-7)
About RAG-17
RAG-17 is a novel, Phase II siRNA therapeutic targeting the SOD1 mRNA transcript. By leveraging the SCAD™ (Smart Chemistry-Aided Delivery) platform, RAG-17 is designed to silence the production of toxic mutant SOD1 protein in the CNS with high potency and extended durability, reducing the need for frequent intrathecal injections.
About Ractigen Therapeutics
Ractigen Therapeutics is a clinical-stage biopharmaceutical company innovating next-generation RNA therapeutics, with a primary focus on small activating RNAs (saRNAs) developed through its clinically validated RNA activation (RNAa) technology. Leveraging proprietary delivery platforms such as SCAD™, LiCO™, and GLORY™, Ractigen is advancing a robust pipeline addressing unmet medical needs in oncology, neurological diseases, and genetic disorders. Its versatile technologies also enable the rapid development of RNA-based solutions, including siRNAs, where applicable, to target life-threatening, fast-progressing conditions such as those in the CNS. Committed to scientific excellence and patient-centered innovation, Ractigen strives to transform healthcare through the power of RNA therapeutics. For more information, visit www.ractigen.com.
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