Myotonic dystrophy type 1 (DM1) is the most common inherited form of muscular dystrophy in adults, caused by a CTG-repeat expansion in the DMPK gene that produces toxic RNA foci, sequesters MBNL splicing factors, and drives the multisystem phenotype that includes progressive muscle weakness, myotonia, cardiac conduction defects, and cognitive change. The disease has no approved disease-modifying therapy, and the most promising candidates in 2026 use peptide-conjugated oligonucleotides to target the toxic RNA directly.
Two programs anchor the peptide pipeline. PepGen's PGN-EDODM1 uses the company's Enhanced Delivery Oligonucleotide platform; the first 5 mg/kg cohort of FREEDOM2-DM1 read out in May 2026 with 7.3% mean splicing correction in six patients, and the company pivoted its full focus to DM1 after a 0.59% dystrophin reading killed its Duchenne program. Vertex's VX-670 pairs a cyclic peptide carrier with an antisense oligonucleotide and is on track for a GALILEO Phase 1/2 readout in the second half of 2026.
Stories here cover DM1 trial readouts, splicing-biology updates, and the broader peptide-oligonucleotide-conjugate modality. See #pepgen, #dm1, and #peptide-oligonucleotide-conjugate for adjacent threads.
PepGen reported Q1 2026 results on May 14 with topline data from the Phase 2 FREEDOM2-DM1 5 mg/kg multiple-ascending-dose cohort. PGN-EDODM1 — the company's peptide-conjugated phosphorodiamidate morpholino oligomer for myotonic dystrophy type 1 (DM1) — produced a mean splicing correction of 7.3% in 6 treated patients vs 6.8% in 2 placebo patients, with no serious adverse events and mainly mild treatment-emergent adverse events. The 10 mg/kg cohort is fully enrolled with data expected H2 2026; the 12.5 mg/kg cohort readout is expected in 2027. PepGen received regulatory clearance to initiate FREEDOM2 sites in South Korea, Australia, and New Zealand to add to existing sites in Canada and the UK. Q1 net loss of $17.8M (vs $30.2M a year earlier); $132.3M cash supports operations through the 12.5 mg/kg MAD readout into 2H 2027. The DM1 program is PepGen's lead clinical asset following the April DMD program discontinuation; it competes with Vertex/Entrada's VX-670 cyclic peptide-oligonucleotide (GALILEO Phase 1/2, H2 2026 readout).
PepGen announced in May 2026 a strategic pivot away from Duchenne muscular dystrophy after the 10 mg/kg cohort of CONNECT1-EDO51 produced only 0.59% of normal dystrophin levels in four patients — well below the threshold of clinical meaningfulness. The company will discontinue DMD program development and focus on the FREEDOM2-DM1 Phase 2 program in myotonic dystrophy type 1, with 5 mg/kg cohort data anticipated. PepGen's Enhanced Delivery Oligonucleotide (EDO) platform conjugates peptide carriers to phosphorodiamidate morpholino oligomers (PMOs) for tissue-targeted delivery. The DM1 program competes with Vertex's VX-670 cyclic peptide-oligonucleotide conjugate (GALILEO Phase 1/2, H2 2026 readout) and Sarepta/Avidity Biosciences in the same indication.
Vertex Pharmaceuticals' Q1 business update confirmed continued enrollment and dosing in the multiple-ascending-dose portion of GALILEO, the global Phase 1/2 study of VX-670 in adults with myotonic dystrophy type 1, with results guided for H2 2026. VX-670 is an oligonucleotide linked to a cyclic peptide endosomal-escape vehicle from Entrada Therapeutics' EEV platform; the oligonucleotide engages CUG-repeat RNA to liberate bound MBNL1 splicing factor and correct the upstream missplicing that drives DM1 pathology. The trial is the first clinical readout for the Vertex–Entrada DM1 collaboration, originally signed February 2023 with $250M upfront. DM1 has no disease-modifying therapy.