Ractigen Therapeutics presented positive first-in-human clinical data for its RNA activation therapeutic, RAG-18, at the World Muscle Society 2026 congress. The Phase I trial in boys with Duchenne muscular dystrophy demonstrated the first clinical proof-of-mechanism for RNA activation in a monogenic disease. Results from Cohort 1 showed a 3.5- to 5.3-fold upregulation of sarcolemmal utrophin, improved muscle architecture, and a favorable safety profile with zero serious adverse events.
RAG-18 Phase I trial results
- ▪The Phase I trial of RAG-18 evaluated safety, tolerability, pharmacodynamics, and exploratory efficacy in ambulatory boys aged 4 to 15 with genetically confirmed Duchenne muscular dystrophy.
- ▪Ractigen Therapeutics presented positive first-in-human clinical data from its ongoing Phase I trial of RAG-18 at the 31st Annual Congress of the World Muscle Society in Hiroshima, Japan.
- ▪Cohort 2 of the RAG-18 Phase I trial, evaluating a 30 mg monthly intravenous dose, is fully enrolled with safety follow-up ongoing as of October 5, 2026.
RNA activation proof-of-mechanism
- ▪The Phase I trial of RAG-18 demonstrated that systemically delivered small activating RNA can safely enter human skeletal muscle and upregulate an endogenous target protein.
- ▪The Phase I trial data for RAG-18 established the first clinical proof-of-mechanism for RNA activation in a human monogenic disease.
Sarcolemmal utrophin upregulation
- ▪Immunofluorescence analysis of muscle biopsies at Day 113 in the RAG-18 trial confirmed precise and uniform localization of upregulated utrophin to the sarcolemma.
- ▪Paired muscle biopsies from three participants in Cohort 1 of the RAG-18 trial showed a 3.5- to 5.3-fold upregulation of sarcolemmal utrophin signal density in mature myofibers at Day 113.
Muscle tissue histopathological remodeling
- ▪Quantitative muscle MRI in the RAG-18 trial revealed reductions in thigh muscle T2 relaxation times of up to 11.6% at Day 169, indicating a reduction of active tissue edema.
- ▪Morphometric analysis at Day 113 of the RAG-18 trial showed increased mean myofiber cross-sectional area of 5% to 15% and increased mean myofiber diameter of 5.34 to 27.50 micrometers.
- ▪Muscle biopsies at Day 113 of the RAG-18 trial showed a decrease in muscle fat fraction of 3% to 10% without drug-induced myonecrosis or inflammation.
Zero serious adverse events
- ▪All reported adverse events in Cohort 1 of the RAG-18 trial were mild, transient, and resolved spontaneously without requiring dose reductions or discontinuations.
- ▪The Phase I trial of RAG-18 reported zero dose-limiting toxicities, zero serious adverse events, and no treatment-emergent adverse events of Grade 3 or higher in Cohort 1.
Mutation-independent DMD treatment approach
- ▪Utrophin is a structural homolog of dystrophin that can substitute for dystrophin at the muscle membrane, making its upregulation a mutation-independent therapeutic strategy for Duchenne muscular dystrophy.
- ▪The three participants treated in Cohort 1 of the RAG-18 trial carried three different types of Duchenne muscular dystrophy mutations, yet all showed positive therapeutic signals.
Debatable claims
- ▪Non-viral RNA activation is superior to viral-vector gene therapies for muscular dystrophy
- ▪Mutation-independent therapies should be prioritized over mutation-specific treatments for Duchenne muscular dystrophy
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