PGN-EDO51 for the Treatment of Duchenne Muscular Dystrophy Demonstrates Higher Levels of Exon Skipping in Phase II Trial

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PepGen has shared positive data from the CONNECT1-EDO51 Phase II trial (NCT06079736) of its lead investigational candidate, PGN-EDO51 for patients with Duchenne muscular dystrophy (DMD) whose mutations are amenable to an exon 51-skipping approach.¹

While the study is still ongoing, data show the investigational therapy demonstrated higher levels of exon skipping than previously reported studies with other oligonucleotide therapies at similar PMO dose levels in DMD patients. Additionally, PepGen reports that change from baseline in total dystrophin production and muscle-adjusted dystrophin production was comparable to, or higher than, previously reported studies with other oligonucleotide therapies at similar PMO dose levels in DMD patients.

The 5 mg/kg dose from the first dose cohort was well tolerated and all patients advanced to the long-term extension portion of the trial. The second cohort, which is currently ongoing, is evaluating PGN-EDO51 at an elevated dose of 10 mg/kg.

“We are encouraged by the early data from our CONNECT1 clinical trial of PGN-EDO51 in people with DMD. In three months, the starting monthly dose of 5 mg/kg achieved high levels of exon skipping and all patients showed increases in dystrophin. PGN-EDO51 produced meaningfully higher levels of exon skipped transcript at lower doses and in a shorter time period compared to other exon 51 therapies, approved and in development, indicating that our Enhanced Delivery Oligonucleotide technology is delivering higher levels of oligonucleotide to the nuclei,” James McArthur, PhD, president and CEO of PepGen said in a press release. “Importantly, PGN-EDO51 has demonstrated a favorable safety profile, supporting our ongoing evaluation of the 10 mg/kg monthly dose cohort in CONNECT1. We intend to leverage the early observations from CONNECT1 to optimize our CONNECT2-EDO51 Phase II trial. Based on these initial results, we are optimistic about the possibility that higher levels of dystrophin production will be observed in the 10 mg/kg cohort of CONNECT1. We also look forward to reporting data from the first cohort of our placebo-controlled multinational study CONNECT2.”

CONNECT1-EDO51 is an open-label, multiple ascending dose trial. It is evaluating PGN-EDO51 at up to three different doses starting with 5 mg/kg administered intravenously once every four weeks for 12 weeks. The key endpoints for the study are safety, dystrophin production, and exon skipping.

According to the National Organization for Rare Disorders, DMD affects approximately 1 in 3,500 male births worldwide. The muscle disorder is typically recognized between the ages of three and six.²

In the press release, Hugh McMillan, MD, pediatric neurologist at the Children’s Hospital of Eastern Ontario, and professor in the department of pediatrics at the University of Ottawa added: “People with DMD and their families constantly hope for effective therapies with the potential to change the course of this relentlessly progressive neuromuscular disease. I was pleased to see that the 5 mg/kg dose was well tolerated and that all three participants demonstrated an increase in dystrophin production and exon skipping after only three months of treatment with PGN-EDO51. I look forward to seeing the results of exon skipping and dystrophin production at 10 mg/kg in both CONNECT1 and CONNECT2.”

References

1. PepGen Announces Positive Data from Low-Dose Cohort of PGN-EDO51 in Ongoing CONNECT1-EDO51 Phase 2 Clinical Trial for Treatment of Duchenne Muscular Dystrophy. News release. PepGen. July 30, 2024. Accessed July 31, 2024. https://investors.pepgen.com/news-releases/news-release-details/pepgen-announces-positive-data-low-dose-cohort-pgn-edo51-ongoing

2. Duchenne Muscular Dystrophy. National Organization for Rare Disorders. July 15, 2024. Accessed July 31, 2024. https://rarediseases.org/rare-diseases/duchenne-muscular-dystrophy/