Ractigen's RAG-17 Shows 81% Reduction in Neurodegeneration Biomarker in SOD1-ALS Phase I Trial
核心洞察
Ractigen Therapeutics reported positive Phase I data for RAG-17, a novel siRNA therapeutic targeting SOD1-ALS (搜索), demonstrating an 81% reduction in plasma neurofilament light chain (搜索) levels.
The single intrathecal dose showed favorable safety profile with no serious adverse events and achieved 58.1% reduction in cerebrospinal fluid SOD1 (搜索) protein by Day 90.
Preliminary clinical data from the highest dose cohort showed functional stabilization with zero decline in ALSFRS-R scores at Day 90 in all assessed participants.
Ractigen Therapeutics announced positive preliminary data from its Phase I trial of RAG-17, a novel small interfering RNA (siRNA) therapeutic targeting amyotrophic lateral sclerosis (搜索) (ALS) patients with superoxide dismutase 1 (搜索) (SOD1 (搜索)) gene mutations. The data, presented at the 2026 American Academy of Neurology Annual Meeting, demonstrated an unprecedented 81% reduction in plasma neurofilament light chain (搜索) (NfL) levels alongside a favorable safety profile.
Significant Biomarker Reductions Observed
The randomized, double-blind, placebo-controlled single ascending dose phase evaluated 20 participants across five sequential dose cohorts (30, 90, 120, 150, and 180 mg) with a 3:1 randomization ratio. RAG-17 demonstrated profound target engagement, with a single intrathecal dose yielding rapid and durable reductions in the disease-driving protein.
In the 150 mg cohort, the maximum reduction in cerebrospinal fluid SOD1 (搜索) reached 58.1% by Day 90, maintaining clinically meaningful reduction through Day 210. The 180 mg cohort showed the most dramatic results, with plasma NfL levels dropping by 81.2% from baseline by Day 150. Neurofilament light chain (搜索) serves as a critical marker of neuroaxonal damage in ALS patients.
Favorable Safety Profile and Clinical Stabilization
RAG-17 was well-tolerated across all ascending dose cohorts with no serious adverse events or Grade 3 treatment-emergent adverse events reported. Only three treatment-related adverse events were documented, all classified as mild.
Functional assessment using the ALS Functional Rating Score-Revised (ALSFRS-R) in the 180mg cohort revealed encouraging clinical stabilization signals. At Day 90, all participants with baseline and post-dosing assessments (n=3) exhibited zero functional decline. At Day 150, decreases remained minimal, ranging from 0 to 4 points.
SCAD Technology Platform
RAG-17 utilizes Ractigen's proprietary Smart Chemistry-Aided Delivery (SCAD™) technology, which conjugates the siRNA duplex to an accessory oligonucleotide. This innovative architecture enables widespread central nervous system distribution and exceptionally durable target engagement following a single intrathecal injection, potentially allowing for significantly extended dosing intervals compared to current therapies.
"Achieving an 81% reduction in plasma NfL—a critical marker of neuroaxonal damage—alongside a highly favorable safety profile from a single administration is unprecedented," said Dr. Long-Cheng Li, CEO of Ractigen Therapeutics. "Furthermore, the early signals of clinical stabilization we are observing at the highest dose level strongly validate our SCAD platform."
Phase II Trial Advancement
Following these encouraging results, Ractigen has initiated a Phase II clinical trial for RAG-17. The randomized, double-blind, placebo-controlled, multiple ascending dose study is designed to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of repeated intrathecal injections in patients with SOD1 (搜索) mutations.
Since the first participant was dosed on January 13, 2026, enrollment for two cohorts has been completed. The trial is being conducted across multiple sites in China, led by investigators including Dr. Yilong Wang at Beijing Tiantan Hospital and Dr. Zhi-Ying Wu at the Second Affiliated Hospital of Zhejiang University School of Medicine.
Addressing Unmet Medical Need
SOD1 (搜索) gene mutations account for approximately 10-30% of familial ALS cases and about 1-2% of sporadic ALS cases. ALS is a progressive neurodegenerative disease affecting nerve cells in the brain and spinal cord, leading to muscle weakness, paralysis, and typically death within three to five years of diagnosis.
"SOD1-ALS (搜索) is a genetically defined disease with a clear biological target, yet patients still face a very limited treatment landscape," commented Dr. Zhi-Ying Wu, Principal Investigator. "What we observed in this Phase I study—a substantial and durable reduction in CSF SOD1 (搜索) protein after a single dose, accompanied by a profound decrease in plasma NfL and early stabilization of functional scores in the highest dose group—gives us strong reason for optimism."
RAG-17 has received Orphan Drug Designation from the U.S. Food and Drug Administration and has been selected for the CARE Program of China's National Medical Products Administration, which facilitates accelerated development of rare disease therapies.