Sarepta reports SRP-1003 DM1 preclinical data

• Sarepta Therapeutics (NASDAQ:SRPT) presented new preclinical data showing that investigational SRP-1003 can reduce disease-causing DMPK transcripts associated with myotonic dystrophy type 1 (DM1).
• The siRNA program demonstrated activity within the nucleus, where the toxic RNA drivers of DM1 pathology originate.
• Sarepta said the findings support continued advancement of SRP-1003 in its ongoing Phase 1/2 clinical study.

Sarepta Therapeutics (NASDAQ:SRPT) presented new preclinical findings from its SRP-1003 program at the 22nd Annual Meeting of the Oligonucleotide Therapeutics Society (OTS).

The investigational small interfering RNA (siRNA) therapy is being developed for myotonic dystrophy type 1 (DM1), a genetic disorder caused by toxic RNA accumulation from mutations in the DMPK gene.

The company reported that SRP-1003 directly reduced pathogenic DMPK transcripts within both nuclear and cytoplasmic compartments.

In patient-derived muscle cells, SRP-1003 produced dose-dependent reductions in DMPK RNA, achieving up to approximately 80% knockdown in both compartments.

Sarepta said functional evidence of nuclear activity was demonstrated through correction of muscleblind-like (MBNL)-dependent mis-splicing, a process disrupted by toxic DMPK RNA in DM1.

The results were confirmed using multiple independent methods, including RNA fluorescence in situ hybridization (RNA FISH), compartment-fractionated digital PCR, and in situ RNAscope analysis.

In preclinical DM1 mouse models, SRP-1003 reduced toxic nuclear RNA foci in skeletal muscle, diaphragm, and heart tissue, while lowering human and mouse DMPK RNA levels.

The company also reported sustained muscle exposure for up to 16 weeks following a single intravenous dose in preclinical pharmacokinetic studies.

SRP-1003 is currently being evaluated in a first-in-human Phase 1/2 randomized, placebo-controlled clinical trial in adults with DM1. Sarepta expects to share clinical results later in 2026.

Sarepta Therapeutics develops precision genetic medicines for rare diseases, including therapies targeting muscular and neuromuscular disorders.