Ractigen Therapeutics presented first-in-human data from an ongoing Phase I trial of RAG-18 at the 31st annual congress of the World Muscle Society in Hiroshima, the company said. The open-label, dose-escalation study is evaluating the safety, tolerability, pharmacodynamics and exploratory efficacy of the therapy in ambulatory boys aged 4 to 15 with genetically confirmed Duchenne muscular dystrophy. The presentation covered data through Day 169 from Cohort 1, in which three participants received 15 mg monthly by intravenous infusion. Ractigen described the results as the first clinical proof-of-mechanism for RNA activation in a human monogenic disease.
No dose-limiting toxicities and no serious adverse events were reported, and there were no treatment-emergent adverse events of Grade 3 or higher. All adverse events reported were mild, transient and resolved without medical intervention, with no dose interruptions, reductions or discontinuations.
Paired contralateral muscle biopsies taken at Day 113 and analysed by whole-field quantitative immunofluorescence showed 3.5- to 5.3-fold increases in sarcolemmal utrophin signal density in mature myofibers, and a 4.1- to 4.7-fold increase in regenerating myofibers, against pre-dose baseline. Co-staining with laminin confirmed localization to the sarcolemma. Morphometric analysis showed mean myofiber cross-sectional area up 5% to 15% and mean myofiber diameter up 5.34 to 27.50 micrometres, with no evidence of drug-induced myonecrosis or inflammation, while muscle fat fraction fell by 3% to 10%. Quantitative muscle MRI showed reductions in thigh muscle T2 relaxation times of up to 11.6% at Day 169.
On function, all three participants showed positive numerical trends in spirometric parameters over 24 weeks, with percent predicted forced vital capacity rising by 2.8% to 41.0% and forced expiratory volume by 2.8% to 34.0%. In an early-ambulatory participant aged 6.8, six-minute walk distance improved by 36.5 m, while in a late-ambulatory participant aged 12.7 it was preserved, a change of minus 1.0 m, alongside an improved four-stair climb time. A third participant, aged 7.3, recorded a decline of 62.5 m. NSAA scores declined by 3 points in all three participants. Left ventricular ejection fraction remained within normal limits in all participants through the 24-week follow-up.
Cohort 2, at 30 mg monthly, is fully enrolled and safety follow-up is ongoing as planned. The study's principal investigator, Yi Dai of Peking Union Medical College Hospital, said the three boys carried three different types of DMD mutation yet all showed signals in the same direction. Ractigen founder and chief executive Long-Cheng Li said the data showed saRNA could activate an endogenous target gene in human skeletal muscle, and that with Cohort 2 fully enrolled the company was committed to accelerating clinical development.
