Ractigen’s SOD1-ALS siRNA Therapy RAG-17 Shows Significant SOD1 Reduction and Favorable Safety in Phase 1, Published in Nature Medicine

July 19, 2026

BioSpace USA

Overview

Ractigen Therapeutics published preclinical and positive First-in-Human Phase 1 clinical data for RAG-17, an siRNA therapy for SOD1-ALS, in Nature Medicine. The trial met primary safety endpoints with no serious adverse events, demonstrating significant reductions in CSF SOD1 protein and plasma NfL. Utilizing Ractigen’s proprietary Smart Chemistry-Aided Delivery (SCAD™) technology, RAG-17 achieved broad CNS distribution and durable gene silencing, marking a critical advance for RNAi therapeutics in neurodegenerative diseases.

In Depth

Key Findings

Ractigen Therapeutics has announced the publication of landmark preclinical pharmacology, non-human primate target engagement, and positive First-in-Human Phase 1 clinical data for RAG-17, an siRNA therapy developed for SOD1-ALS, in Nature Medicine. The Phase 1 trial successfully met its primary safety endpoints, reporting no serious adverse events. Crucially, the study demonstrated significant reductions in both cerebrospinal fluid (CSF) SOD1 protein and plasma neurofilament light chain (NfL), indicating a potential disease-modifying effect.

Technical / Clinical Details

RAG-17 is an siRNA designed to silence the SOD1 gene, which is implicated in a severe form of Amyotrophic Lateral Sclerosis (ALS). Preclinical studies, including those in non-human primates, established that RAG-17 achieved broad central nervous system (CNS) distribution and durable gene silencing of its target mRNA. This extensive delivery and sustained effect are attributed to Ractigen’s proprietary Smart Chemistry-Aided Delivery (SCAD™) technology. SCAD™ involves specific chemical modifications to the siRNA molecule, enhancing its stability in vivo, facilitating its passage across the blood-brain barrier, and ensuring efficient uptake by target cells. The observed reductions in CSF SOD1 protein and plasma NfL in the Phase 1 trial are significant, as these are recognized biomarkers for disease progression in ALS, suggesting that RAG-17 may indeed be slowing the neurodegenerative process.

Background & Context

ALS is a rapidly progressive and fatal neurodegenerative disease with limited treatment options, particularly for genetic forms like SOD1-ALS. RNA interference (RNAi) therapeutics offer a powerful approach to precisely inhibit the expression of specific disease-causing genes. However, delivering RNAi molecules effectively to the CNS has historically been a major challenge due due to the blood-brain barrier. Ractigen’s SCAD™ technology represents a significant breakthrough in overcoming these delivery hurdles, demonstrating the feasibility of effective RNAi therapy for CNS disorders. This advance provides a critical new strategy for addressing previously intractable neurological conditions.

Strategic Significance & Outlook

The positive safety profile and encouraging biomarker data from the RAG-17 Phase 1 trial elevate expectations for its subsequent larger-scale clinical development. Ractigen plans to progress RAG-17 into Phase 2 and 3 trials, aiming to establish it as a potentially first-in-class disease-modifying therapy for SOD1-ALS patients who currently face a dire prognosis. The success of RAG-17 could have far-reaching implications, not only for ALS but also for the development of RNAi therapeutics for other neurodegenerative diseases, opening new avenues for treatment in areas with high unmet medical need.

Source: https://www.biospace.com/press-releases/ractigen-therapeutics-announces-landmark-publication-in-nature-medicine-highlighting-unprecedented-preclinical-efficacy-and-positive-first-in-human-clinical-data-for-rag-17-in-sod1-als

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