UK MHRA Clears PepGen's Phase 2 CONNECT2-EDO51 Trial for DMD Treatment PGN-EDO51

PepGen Inc., a clinical-stage biotechnology firm, has received approval from the UK Medicines & Healthcare products Regulatory Agency (MHRA) to commence a Phase 2 clinical trial for its drug candidate PGN-EDO51. The trial, known as CONNECT2-EDO51, is designed for patients with Duchenne muscular dystrophy (DMD) who can benefit from an exon 51-skipping treatment.

The company's President and CEO, James McArthur, expressed enthusiasm for advancing PGN-EDO51, which is considered a potentially transformative therapy for DMD patients. The MHRA's authorization to proceed with the trial is a significant milestone in the development of this treatment. The ongoing CONNECT1-EDO51 trial, along with the upcoming CONNECT2-EDO51 study, may provide the necessary data to support an accelerated approval for PGN-EDO51, pending alignment with regulatory bodies.

The Phase 2 trial is structured as a multinational, randomized, double-blind, placebo-controlled study involving multiple ascending doses. It aims to enroll around 20 boys and young men with DMD who are at least six years old and suitable for exon 51-skipping. Participants will receive either PGN-EDO51 or a placebo over a 24-week period, with the dosage starting at 5 mg/kg and potentially increasing to 10 mg/kg or higher, based on safety data from previous cohorts. The trial will include muscle biopsies and will evaluate the drug's effect on exon skipping, dystrophin production, and overall safety and tolerability. An open-label extension will be available for all participants.

PGN-EDO51 is PepGen's lead clinical candidate for DMD treatment, utilizing the company's proprietary Enhanced Delivery Oligonucleotide (EDO) technology. This technology is designed to deliver a therapeutic oligonucleotide that targets the underlying cause of DMD. The drug is intended to skip exon 51 of the dystrophin transcript, which could restore the open reading frame and allow for the production of a functional, albeit truncated, dystrophin protein. In preclinical studies, PGN-EDO51 demonstrated higher levels of exon 1 skipping compared to other similar treatments, suggesting the potential for increased dystrophin production in patients.

DMD is a progressive, muscle-wasting disease that primarily affects boys and is caused by mutations in the dystrophin gene. It is one of the most common rare genetic diseases, with an incidence rate of about one in every 3,500 to 5,000 male births. The disease leads to progressive muscle weakness, loss of mobility, and can result in cardiac and respiratory complications, ultimately proving fatal by early adulthood. Despite advancements in treatment, current exon skipping therapies have limitations due to poor muscle tissue delivery and have yet to provide significant clinical benefits for DMD patients.

PepGen's EDO platform is the result of over a decade of research and development, focusing on cell-penetrating peptides to enhance the uptake and activity of oligonucleotide therapeutics. The company is committed to developing a pipeline of therapeutic candidates targeting the root causes of severe diseases.