First Patient Receives PGN-EDO51 in Phase 2 DMD Trial

PepGen Inc., a company focused on developing innovative therapies for severe neuromuscular and neurological conditions, has initiated a Phase 2 clinical trial for PGN-EDO51, a potential treatment for Duchenne muscular dystrophy (DMD). The CONNECT1-EDO51 trial is an open-label, multiple ascending dose study that has dosed its first patient. The trial aims to assess the safety and efficacy of PGN-EDO51 in DMD patients who are candidates for exon 51 skipping therapy.
In a previous Phase 1 study involving healthy volunteers, PGN-EDO51 showed a peak exon 51 skipping of 3.8%, with all participants exhibiting exon skipping. The drug was well-tolerated, and it outperformed other exon 51 skipping treatments in terms of skipping levels. The Phase 2 trial will evaluate the drug's safety, muscle concentrations of the oligonucleotide, exon skipping, and dystrophin protein production after four monthly doses.
PGN-EDO51 leverages PepGen's proprietary Enhanced Delivery Oligonucleotide (EDO) technology, which is designed to deliver therapeutic oligonucleotides directly to the target cells. The drug is intended to skip exon 51 in the dystrophin gene, potentially restoring the reading frame and allowing for the production of a functional, albeit shortened, dystrophin protein. This approach targets approximately 13% of DMD patients.
Duchenne muscular dystrophy is a genetic disorder that leads to progressive muscle degeneration and is typically fatal by early adulthood. Current treatments for DMD have limitations, particularly in their ability to effectively deliver therapeutics to muscle tissue.
PepGen's EDO platform is based on over ten years of research and uses cell-penetrating peptides to enhance the delivery and efficacy of oligonucleotide therapeutics. The company is committed to advancing a new generation of therapies for serious diseases with unmet medical needs.

DMD is a severe X-linked recessive disorder that primarily affects males and results from mutations in the dystrophin gene, which is essential for muscle health. It is one of the most common rare genetic diseases, with a high incidence rate. The condition is marked by a progressive loss of muscle strength, leading to a decline in mobility and life-threatening complications.

PepGen is a clinical-stage biotech firm dedicated to creating next-generation oligonucleotide therapies for severe neuromuscular and neurological diseases. The company's EDO platform is the result of extensive R&D and utilizes cell-penetrating peptides to boost the uptake and effectiveness of oligonucleotide treatments. PepGen is developing a range of therapeutic candidates aimed at addressing the underlying causes of serious diseases.

The company's lead candidate, PGN-EDO51, has shown promising preclinical results, including higher levels of exon 51 skipping in non-human primates compared to other therapeutic candidates. In human trials, it demonstrated a significantly higher exon 51 skipping rate compared to a naked oligonucleotide.

The Phase 2 CONNECT1-EDO51 clinical trial will involve approximately 10 male patients aged 8 and above with DMD amenable to exon 51 skipping. The study will assess the safety and tolerability of PGN-EDO51, with the starting dose escalating from 5 mg/kg to 10 mg/kg based on safety data from previous cohorts.

The trial's preliminary data, including initial safety, exon 51 skipping, and dystrophin protein production, is anticipated in mid-2024. The results of the Phase 1 study in healthy volunteers were encouraging, with peak exon 51 skipping of 3.8% observed at a single dose of 10 mg/kg.

PepGen's President and CEO, James McArthur, Ph.D., expressed optimism about the potential of PGN-EDO51 to improve the lives of DMD patients, based on the exon skipping levels achieved in the Phase 1 trial. The company is looking forward to the initial data readout for the 5 mg/kg PGN-EDO51 dose level in mid-2024.

PGN-EDO51 is designed to address the root cause of DMD by skipping exon 51 of the dystrophin transcript, aiming to restore the open reading frame and enable the production of a functional, albeit truncated, dystrophin protein. The drug has shown high levels of exon 51 skipping in preclinical studies and in human trials, indicating its potential to significantly improve dystrophin production in patients.

DMD is a devastating disease with no cure, and current exon skipping therapies have yet to provide meaningful clinical benefits due to delivery challenges. PepGen's EDO technology aims to overcome these limitations and transform the treatment landscape for DMD patients.