PepGen to discontinue DMD programs after PGN-EDO51 did not achieve target

PepGen (PEPG) announced that based on the levels of dystrophin protein measured in the 10 mg/kg cohort of its CONNECT1-EDO51 study investigating PGN-EDO51 in Duchenne muscular dystrophy patients amenable to exon 51 skipping, the company will focus on advancing its “promising” myotonic dystrophy type 1 program currently in Phase 2 clinical development. The company is voluntarily discontinuing development of PGN-EDO51 and intends to wind down all DMD-related research and development activities. In the 10 mg/kg cohort of the CONNECT1 study, PGN-EDO51 increased exon 51 skipped transcripts to 4.26%; however, total dystrophin only increased to 0.59% of normal levels. The safety profile of PGN-EDO51 continued to be generally favorable and all treatment-related adverse events were mild in nature. No serious adverse events were reported in the study. “We are disappointed by the dystrophin results observed in the 10 mg/kg dose cohort in CONNECT1, as it was our hope that we could improve upon existing therapies for patients in a more profound way,” said James McArthur, PhD, President and CEO of PepGen. “As we wind down our DMD program, we would like to thank the patients, families, caregivers, investigators and study staff for their support and participation in this research. I also want to acknowledge our team’s hard work and commitment to advancing new potential treatments for DMD patients.” PepGen continues to expect to report data from its FREEDOM-DM1 15 mg/kg cohort in patients with DM1 during the second half of 2025. FREEDOM is a Phase 1 single ascending dose, randomized, placebo-controlled clinical trial, with endpoints including safety, 28-day splicing correction and functional benefit measures. The company also continues to expect to report data from the 5 mg/kg cohort of its FREEDOM2-DM1 study in DM1 patients in the first quarter of 2026. FREEDOM2 is a Phase 2 multiple ascending dose, randomized, placebo-controlled clinical trial, with endpoints following four doses that include safety, splicing correction and functional benefit measures.