RAG-17 Shows Early Safety and Biomarker Improvements in Phase 1 Study of SOD1-ALS

Researchers recently presented preliminary data from the single ascending dose (SAD) phase 1 portion of an ongoing phase 1/2 study (NCT06556394) testing Ractigen’s investigational small interfering RNA (siRNA) therapy RAG-17. All told, the findings showed that treatment with the agent demonstrated favorable safety and tolerability, along with reductions in key biomarkers of neurodegeneration, in patients with superoxide dismutase 1 (SOD1)–associated amyotrophic lateral sclerosis (ALS).¹

In the randomized, double-blind, placebo-controlled SAD portion of the ongoing trial, 20 participants were enrolled across 5 sequential dose cohorts (30, 90, 120, 150, and 180 mg) and randomized in a 3:1 ratio to receive RAG-17 or placebo. The company noted that since the study remains ongoing, the results, presented at the 2026 American Academy of Neurology (AAN) Annual Meeting, held April 18–22 in Chicago, Illinois, were reported in a blinded manner.

Pharmacodynamic analyses demonstrated evidence of target engagement following a single intrathecal dose. In the 150 mg cohort, cerebrospinal fluid SOD1 levels were reduced by a maximum of 58.1% (blinded analysis) by Day 90, with reductions maintained through Day 210. Investigators also reported reductions in neurodegeneration biomarkers. In the 180 mg cohort, plasma neurofilament light chain levels decreased by 81.2% from baseline (blinded analysis) by Day 150, indicating a marked reduction in a biomarker associated with neuroaxonal injury.

"The data presented at AAN this year represents a major milestone for Ractigen and, more importantly, for patients living with SOD1-ALS," Long-Cheng Li, MD, CEO of Ractigen Therapeutics, said in statement.¹ "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. Furthermore, the early signals of clinical stabilization we are observing at the highest dose level strongly validate our SCAD platform. We are thrilled to have already initiated dosing in the Phase II portion of the study to further evaluate RAG-17's transformative potential."

Exploratory clinical outcomes were also assessed using the ALS Functional Rating Scale–Revised in the 180 mg cohort. Among participants with baseline and at least 1 postdose assessment (n = 3), no functional decline (0-point change from baseline) was observed at Day 90. At Day 150, researchers observed that the changes in ALSFRS-R scores ranged from 0 to 4 points, suggesting a limited degree of functional decline in this small subgroup.

READ MORE: Nipocalimab Shows Sustained Disease Control and Symptom Improvement in 2-Year Extension Study

In terms of safety, findings showed that RAG-17 was well tolerated across all dose levels, with no reported serious adverse events (AEs) or Grade 3 treatment-emergent AEs. A total of 3 treatment-related AEs were observed, all of which were mild in severity. Notably, no dose-limiting toxicities were reported.

"SOD1-ALS is a genetically defined disease with a clear biological target, yet patients still face a very limited treatment landscape," Zhi-Ying Wu, MD, PhD, principal investigator at the Second Affiliated Hospital Zhejiang University School of Medicine, said in a statement.¹ "What we observed in this Phase I study—a substantial and durable reduction in CSF SOD1 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. These data clearly suggest that RAG-17 is engaging its target in a highly meaningful way, and we look forward to generating further evidence in the ongoing Phase II study."

RAG-17 is designed using Ractigen Therapeutics’ proprietary Smart Chemistry-Aided Delivery platform, which conjugates the siRNA duplex to an accessory oligonucleotide. This approach is intended to enhance central nervous system distribution and support sustained target engagement following a single intrathecal administration, with the potential to extend dosing intervals relative to existing therapies.

Ractigen Therapeutics also reported that a phase 2 randomized, double-blind, placebo-controlled, multiple ascending dose study of RAG-17 is underway to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of repeated intrathecal administration in patients with SOD1 mutations. The first participant was dosed on January 13, 2026, and enrollment in 2 cohorts has been completed.²

Click here for more coverage of AAN 2026.

REFERENCES
1. Ractigen Therapeutics Presents Positive Phase I Data for RAG-17 in SOD1-ALS at the 2026 AAN Annual Meeting, Demonstrating 81% Reduction in Neurofilament Light Chain. News release. Ractigen Therapeutics. April 21, 2026. Accessed April 28, 2026. https://www.ractigen.com/ractigen-therapeutics-presents-positive-phase-i-data-for-rag-17-in-sod1-als-at-the-2026-aan-annual-meeting-demonstrating-81-reduction-in-neurofilament-light-chain/
2. Ractigen Therapeutics Announces First Patient Dosed in Phase II Clinical Trial of RAG-17 for SOD1-ALS. News release. Ractigen Therapeutics. January 13, 2026. Accessed April 28, 2026. https://www.ractigen.com/ractigen-therapeutics-announces-first-patient-dosed-in-phase-ii-clinical-trial-of-rag-17-for-sod1-als/