Epicrispr's EPI-321 Reaches Full Enrolment for FSHD

EPI-321 is designed to treat the underlying cause of FSHD by durably repressing expression of the DUX4 gene, whose inappropriate activation drives muscle degeneration. Rather than editing DNA, the therapy uses a CRISPR interference (CRISPRi) approach based on CasMINI, a compact, catalytically inactive Cas protein engineered for efficient delivery by a single adeno-associated virus (AAV) vector. Guided to regulatory regions of DUX4 by guide RNAs, CasMINI is fused to epigenetic repressor domains that promote formation of repressive chromatin and silence DUX4 transcription without introducing DNA double-strand breaks or altering the underlying DNA sequence.

According to the company, patients receiving a single intravenous dose showed a favourable safety profile together with statistically significant increases in whole-body lean muscle volume measured by MRI, biomarker changes consistent with DUX4 suppression, and favourable trends in muscle strength and functional outcomes. The dose-escalation phase enrolled 12 adults across two dose levels (2 × 10¹³ and 4 × 10¹³ vg/kg). These findings have not yet been reported in a peer-reviewed publication, and additional clinical data are expected at the World Muscle Society Annual Congress in September 2026.

The announcement was made by Epicrispr Biotechnologies, a clinical-stage biotechnology company based in San Francisco. The update was issued as a company press release on 7 July 2026.