Ractigen Completes Phase 2 Enrollment for RAG-17 in SOD1-ALS

Ractigen Therapeutics announced the completion of patient enrollment and initial dosing across all cohorts of its phase 2 clinical trial evaluating RAG-17, an investigational small interfering RNA (siRNA) therapy targeting superoxide dismutase 1 (SOD1) mutations in amyotrophic lateral sclerosis (ALS).¹

"Completing enrollment and first-dose administration in our Phase II MAD trial marks a pivotal achievement for Ractigen as we advance RAG-17 along a defined, accelerated regulatory pathway," Long-Cheng Li, MD, founder and chief executive officer of Ractigen, said in a statement.¹

Phase 2 trial design

The phase 2 trial (NCT06556394) is a randomized, double-blind, placebo-controlled, multiple ascending dose study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of repeated intrathecal RAG-17 injections in patients with SOD1 mutations. It is being conducted across 5 Chinese sites, including Beijing Tiantan Hospital, West China Hospital of Sichuan University, and the First Affiliated Hospital of Sun Yat-sen University.

With all participants now dosed, the trial enters what Ractigen described as a critical evaluation period, during which safety, biomarker, and functional data will continue to accumulate ahead of upcoming regulatory interactions.

Supporting phase 1 data

RAG-17's development draws on 2 related but distinct phase 1 datasets. The first is a 6-patient, open-label, investigator-initiated dose-escalation study conducted at Beijing Tiantan Hospital, the full results of which were published in Nature Medicine in July 2026 alongside preclinical and non-human primate data.²

That study met its primary safety endpoint, with no serious adverse events, and showed a mean 69% reduction in cerebrospinal fluid (CSF) SOD1 protein by day 240 and a mean 62% reduction in plasma neurofilament light chain (NfL), with individual patients reaching reductions of up to 85% below baseline. Exploratory data also suggested stabilization of respiratory function, measured by percent predicted forced vital capacity, in some participants.

"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," Yilong Wang, MD, corresponding author and principal investigator in the Department of Neurology at Beijing Tiantan Hospital, said in a statement.²

A second, separate dataset came from the single ascending dose (SAD) portion of the current phase 1/2 program, presented at the 2026 American Academy of Neurology Annual Meeting.³ That randomized, double-blind, placebo-controlled cohort enrolled 20 participants across 5 dose levels (30-180 mg) in a 3:1 randomization to RAG-17 or placebo.

In blinded analyses, the 150 mg cohort showed CSF SOD1 reductions of up to 58.1% by day 90, sustained through day 210, while the 180 mg cohort showed an 81.2% mean reduction in plasma NfL by day 150. No serious adverse events or grade 3 treatment-related events were reported, and only 3 mild treatment-related adverse events occurred across all dose levels.³

"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 of Zhejiang University School of Medicine, said in a statement at the time.³

Mechanism and regulatory background

RAG-17 is built on Ractigen's proprietary Smart Chemistry-Aided Delivery (SCAD) platform, which conjugates the siRNA duplex to an accessory oligonucleotide to enhance distribution throughout the central nervous system and extend gene silencing following a single intrathecal dose.³ Preclinical data published in 2023 showed that RAG-17 significantly slowed disease progression and extended survival in SOD1G93A ALS mice even when administered after symptom onset, a late-stage rescue effect investigators said was uncommon among therapies typically tested pre-symptomatically in that model.⁴

SOD1 mutations account for roughly 10% to 20% of familial ALS cases and 1% to 2% of sporadic cases.¹ RAG-17 has received Orphan Drug Designation from the FDA and has been selected for the CARE Program of China's Center for Drug Evaluation, which is intended to facilitate accelerated development of rare disease therapies.¹

REFERENCES
1. Ractigen Therapeutics Announces Completion of Enrollment and First Dosing in Phase II Clinical Trial of RAG-17 for SOD1-ALS. News release. Ractigen Therapeutics. August 6, 2026. Accessed August 11, 2026. https://www.prnewswire.com/news-releases/ractigen-therapeutics-announces-completion-of-enrollment-and-first-dosing-in-phase-ii-clinical-trial-of-rag-17-for-sod1-als-302844916.html
2. 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. News release. Ractigen Therapeutics. July 15, 2026. Accessed August 11, 2026. https://www.ractigen.com/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/
3. 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 August 11, 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/
4. Duan C, Kang M, Liu K, et al. RAG-17: A Novel siRNA Conjugate Demonstrating Efficacy in Late-Stage Treatment of SOD1G93A ALS mice. bioRxiv. Published online November 23, 2023. doi:10.1101/2023.11.23.568255.