PGN-EDODM1 (PepGen)

PGN-EDODM1 is an investigational peptide-conjugated antisense oligonucleotide (ASO) developed by PepGen Inc. for the treatment of myotonic dystrophy type 1 (DM1). The drug utilizes PepGen's proprietary Enhanced Delivery Oligonucleotide (EDO) platform, which pairs a cell-penetrating peptide with an ASO to improve tissue delivery and cellular uptake, particularly in muscle tissue. PGN-EDODM1 is designed to bind to the toxic CUG repeat expansion in the *DMPK* mRNA transcript. In DM1, these repeats sequester the Muscleblind-like 1 (MBNL1) protein, a critical RNA processing factor, leading to widespread splicing defects. By blocking these toxic repeats, PGN-EDODM1 aims to liberate MBNL1 protein and restore functional downstream splicing and muscle function without degrading the *DMPK* transcript. The drug has received FDA Fast Track and Orphan Drug designations and is currently being evaluated in clinical trials, including the Phase 1 FREEDOM-DM1 study and its open-label extension, FREEDOM-OLE.