Ractigen's RAG-17 cuts SOD1 protein 69% in six-patient ALS trial
Published Phase 1 data show the siRNA candidate hit its safety endpoint with no serious adverse events, while CSF SOD1 fell 69% and plasma NfL fell 62% in a first-in-human cohort of six.
Executive Summary
- A first-in-human trial of Ractigen's siRNA candidate in SOD1-mutant ALS met its safety endpoint and produced large reductions in a disease-driving protein and a marker of nerve damage.
- The data confirm the drug's intrathecal delivery platform can reach and silence its target in the human central nervous system, the mechanistic threshold this stage of testing was designed to clear.
- The trial was built to test safety and biomarker engagement, not functional decline or survival, so whether the biomarker changes translate into slowed disease progression remains open.
- SOD1-ALS is a genetically defined subset of ALS where an antisense oligonucleotide has already reached approval, giving Ractigen a mechanistic precedent to compete against rather than an unvalidated hypothesis to prove from scratch.
The publication
Ractigen Therapeutics disclosed the peer-reviewed Nature Medicine publication of preclinical and first-in-human data for RAG-17 on July 15, 2026, covering the open-label, dose-escalation trial registered as NCT05903690 at Beijing Tiantan Hospital. The study enrolled six patients with confirmed SOD1 gene mutations and amyotrophic lateral sclerosis, testing multiple intrathecal doses of the siRNA candidate for safety, tolerability, pharmacokinetics and pharmacodynamics. RAG-17 uses Ractigen's SCAD conjugate technology, pairing the siRNA duplex with an accessory oligonucleotide intended to distribute the drug through the central nervous system and sustain gene silencing after a single intrathecal injection. Ractigen+1Ractigen Therapeutics Announces Landmark Publication in Nature Medicine Highlighting Unprecedented Preclinical Efficacy and Positive First-in-Human Clinical Data for RAG-17 in SOD1-ALSJul 15, 2026Safety and Tolerability of RAG-17 in the Treatment of Amyotrophic Lateral Sclerosis Patients With SOD1 Gene MutationNCT05903690
The safety readout
The trial met its primary safety endpoint: no serious adverse events occurred, no patient required invasive mechanical ventilation through the data cutoff, and treatment-emergent adverse events were described as mild to moderate, transient and manageable. Dr. Yilong Wang, the trial's principal investigator at Beijing Tiantan Hospital, said the biomarker responses and safety profile observed in the patients, combined with survival findings in animal models, indicate RAG-17 "has the potential to be a best-in-class disease-modifying therapy," a characterization tied to the drug's own program rather than a head-to-head comparison. RactigenRactigen Therapeutics Announces Landmark Publication in Nature Medicine Highlighting Unprecedented Preclinical Efficacy and Positive First-in-Human Clinical Data for RAG-17 in SOD1-ALSJul 15, 2026
The biomarker result
Mean cerebrospinal fluid SOD1 protein fell 69% by Day 240 in Cohort 1, and mean plasma neurofilament light chain, a marker of nerve-cell damage, fell 62%, with individual patients' nadirs reaching 85% below baseline. Ractigen's chief executive, Dr. Long-Cheng Li, said the company is "incredibly encouraged by the reductions in both disease-driving SOD1 protein and neurofilament light chain," a 69% and 62% mean decline, and intends to advance RAG-17 "to bring a highly potent, less frequently dosed treatment option to the SOD1-ALS community," language that signals plans for later-stage testing without a stated timeline. RactigenRactigen Therapeutics Announces Landmark Publication in Nature Medicine Highlighting Unprecedented Preclinical Efficacy and Positive First-in-Human Clinical Data for RAG-17 in SOD1-ALSJul 15, 2026
How it was done
The trial was an open-label, dose-escalation, investigator-initiated study in six patients with SOD1-confirmed ALS, evaluating multiple intrathecal doses of RAG-17 against safety, tolerability, pharmacokinetic and pharmacodynamic endpoints, with biomarker follow-up through Day 240. There was no control arm; the reported reductions in CSF SOD1 and plasma NfL are within-patient changes from baseline in an uncontrolled cohort, and exploratory functional measures, including forced vital capacity, were described qualitatively as stabilized or improved in some patients rather than reported with a summary statistic. Ractigen+1Ractigen Therapeutics Announces Landmark Publication in Nature Medicine Highlighting Unprecedented Preclinical Efficacy and Positive First-in-Human Clinical Data for RAG-17 in SOD1-ALSJul 15, 2026Safety and Tolerability of RAG-17 in the Treatment of Amyotrophic Lateral Sclerosis Patients With SOD1 Gene MutationNCT05903690
The competitive context
SOD1-ALS already has an approved antisense oligonucleotide that established that reducing SOD1 protein production is a viable therapeutic strategy in this genetically defined population, so RAG-17's biomarker reductions replicate a validated mechanistic direction rather than opening an unproven one. Ractigen's own trial and pipeline records show no other RAG-17 program or prior Ractigen trial completions to benchmark against. The registry record for NCT05903690 shows no protocol amendments beyond the initial registration and a single change event since the trial's 2023 start, consistent with a stable, uneventful record for a small investigator-initiated study. NCT05903690Safety and Tolerability of RAG-17 in the Treatment of Amyotrophic Lateral Sclerosis Patients With SOD1 Gene MutationNCT05903690
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