Suzhou, China-based Ractigen Therapeutics presented first-in-human Phase I data for RAG-18, a small activating RNA therapeutic for Duchenne muscular dystrophy (DMD), reporting increased utrophin expression in skeletal muscle in the first three patients treated.
RAG-18 targets regulatory regions of the UTRN gene to increase transcription of endogenous utrophin, a structural homolog of dystrophin that can partially substitute for the missing protein at the muscle membrane. Because the approach does not depend on the underlying DMD mutation, it could potentially be applicable across a broader patient population than mutation-specific exon-skipping therapies.
In Cohort 1 of the open-label, dose-escalation Phase I trial (NCT07282652), three ambulatory boys received 15 mg of RAG-18 by monthly intravenous infusion. Paired muscle biopsies at Day 113 showed 3.5- to 5.3-fold increases in sarcolemmal utrophin signal density versus baseline, while quantitative MRI showed reductions in thigh muscle T2 relaxation times of up to 11.6% by Day 169.
Functional findings were mixed and exploratory. North Star Ambulatory Assessment scores declined by three points in all three participants; 6-minute walk distance increased by 36.5 m in one patient, was essentially stable in another, and declined by 62.5 m in the third.