PepGen Inc., a clinical-stage biotechnology company focused on advancing next-generation oligonucleotide therapies for severe neuromuscular and neurological diseases, has announced recent developments in its CONNECT clinical program evaluating PGN-EDO51 in patients with Duchenne muscular dystrophy (DMD) amenable to an exon 51 skipping approach.

CONNECT1-EDO51, a Phase 2, open-label, multiple ascending dose (MAD) trial, is currently underway in Canada. The study has enrolled two cohorts of boys and young men with DMD suitable for exon 51 skipping. Key endpoints include safety and tolerability, dystrophin production, exon skipping, and muscle tissue drug concentration. The 10 mg/kg cohort is fully enrolled (n=4), while participants in the 5 mg/kg cohort (n=3) continue to receive the same dose in the long-term extension phase. PepGen remains on track to report clinical data from the 10 mg/kg cohort by the end of 2025.

Magnesium levels in two participants from the 10 mg/kg cohort, previously noted to have asymptomatic hypomagnesemia, have returned to baseline with ongoing oral magnesium supplementation. One participant experienced a temporary pause in dosing due to a decrease in estimated glomerular filtration rate (eGFR); however, this did not meet pre-specified criteria for a dose-limiting toxicity. A follow-up nuclear scan confirmed that measured glomerular filtration rate was within normal limits. The participant’s eGFR is improving, and the study investigator is assessing the potential for resuming treatment. PepGen continues to investigate the event and related factors to better understand its clinical significance.

Health Canada has permitted continued dosing at the 5 and 10 mg/kg levels but has requested further information from the Company before allowing additional dose escalation or enrollment. PepGen is actively working with the agency to address these inquiries.

CONNECT2-EDO51, a Phase 2, multinational, double-blind, placebo-controlled MAD trial, is currently open in the United Kingdom. It will enroll boys and young men with DMD amenable to exon 51 skipping, with endpoints including safety, tolerability, dystrophin production, exon skipping, and functional outcomes. In December, PepGen received a clinical hold from the U.S. Food and Drug Administration (FDA) regarding its Investigational New Drug (IND) application to initiate CONNECT2 in the United States. The FDA's concerns relate to supportive data for the proposed dosing levels. PepGen is engaging with the agency to resolve these issues.

Dr. Paul Streck, Chief Medical Officer and Head of R&D at PepGen, noted that as of January 23, 2025, all treatment-related adverse events in CONNECT1 had been mild and that the safety profile of PGN-EDO51 remained encouraging. He highlighted the improvement in renal function observed in the participant from the 10 mg/kg cohort during the dosing pause and reaffirmed the Company’s commitment to rigorous safety monitoring across its clinical programs. Dr. Streck also stated that PepGen looks forward to providing clinical updates from both CONNECT1 and the FREEDOM-DM1 study in myotonic dystrophy type 1 throughout 2025, including initial data from FREEDOM in the first quarter, as well as updates on CONNECT2.

Source: https://www.businesswire.com/news/home/20250129623573/en/PepGen-Announces-CONNECT-Program-Updates