Ractigen Therapeutics, a clinical-stage biopharmaceutical company focused on developing next-generation RNA-based medicines, has announced positive preliminary data from the single ascending dose (SAD) phase 1 portion of its ongoing Phase I/II clinical trial of RAG-17.
RAG-17 is a novel small interfering RNA (siRNA) therapeutic in development for the treatment of amyotrophic lateral sclerosis (ALS) patients with mutations in the superoxide dismutase 1 (SOD1) gene.
The data were presented at the 2026 American Academy of Neurology (AAN) Annual Meeting in Chicago, Illinois. The presentation was delivered by Dr Zhi-Ying Wu, Principal Investigator of the Second Affiliated Hospital Zhejiang University School of Medicine.
RAG-17 utilises Ractigen’s proprietary smart chemistry-aided delivery (SCADâ„¢) technology, which conjugates the siRNA duplex to an accessory oligonucleotide (ACO). This innovative architecture enables widespread central nervous system (CNS) distribution and exceptionally durable target engagement following a single intrathecal (IT) injection, potentially allowing for significantly extended dosing intervals compared to current therapies.
Key highlights from the presentation
The randomised, double-blind, placebo-controlled SAD phase evaluated 20 participants across five sequential dose cohorts (30, 90, 120, 150, and 180 mg). The participants received RAG-17 or placebo at 3:1 ratio. The study is still ongoing, so the results were presented in a blinded way:
- Favourable safety and tolerability: RAG-17 was well-tolerated across all ascending dose cohorts. There were no serious adverse events (SAEs) or Grade3 treatment-emergent adverse events. Only three treatment-related adverse events were reported and all were mild ≥ 3 treatment-emergent adverse events. Only three treatment-related adverse events were reported and all were mild.
- Profound target engagement: a single IT dose yielded rapid and durable reductions in the disease-driving protein. In the 150 mg cohort, the maximum reduction in cerebrospinal fluid (CSF) SOD1 reached 58.1% (blinded analysis) by day 90, maintaining a clinically meaningful reduction through day 210.
- Deep reductions in neurodegeneration biomarkers: RAG-17 induced a progressive and significant reduction in plasma neurofilament light chain (NfL). In the 180 mg cohort, plasma NfL levels dropped by 81.2% (blinded analysis) from baseline by day 150.
- Encouraging clinical stabilisation: functional assessment was conducted with ALS functional rating score-revised (ALSFRS-R) in the 180mg cohort. In this cohort, blinded preliminary data indicated an attenuation of clinical decline:
- At day 90, all the participants who had baseline and at least one assessment after dosing (n=3) exhibited zero functional decline (a 0-point change from baseline).
- At day 150, decreases remained minimal (ranging from 0 to 4 points).
