– PGN-EDO51 did not achieve target dystrophin levels in CONNECT1-EDO51 trial; Company to discontinue development of DMD programs –
– PGN-EDO51 at 10 mg/kg was generally well tolerated; all treatment-related adverse events were mild –
– DM1 program on track to read out FREEDOM-DM1 15 mg/kg cohort in second half of 2025 and FREEDOM2-DM1 5 mg/kg cohort in Q1 2026 –
PepGen Inc., a clinical-stage biotechnology company advancing the next generation of oligonucleotide therapies, today 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 (DMD) patients amenable to exon 51 skipping, the Company will focus on advancing its promising myotonic dystrophy type 1 (DM1) 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 (n=4) of the CONNECT1 study, PGN-EDO51 increased exon 51 skipped transcripts to 4.26% (a mean increase of 3.5%); however, total dystrophin only increased to 0.59% of normal levels (a mean increase of 0.36%). 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.”
Paul Streck, MD, MBA, Executive Vice President, Head of R&D of PepGen continued, “PGN-EDODM1, PepGen’s investigational drug in development for DM1, has already demonstrated robust target engagement after a single 10 mg/kg dose in patients that resulted in mean mis-splicing correction of 29% with a favorable emerging safety profile as of February 24, 2025, the most recent safety update. Mis-splicing is the primary driver of DM1 pathology and currently patients have no approved treatment options for this disabling, life-shortening disorder. Going forward, we will focus our resources on advancing the Company’s ongoing DM1 clinical program along with our research pipeline.”
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.
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