BOSTON, MA, USA I March 04, 2024 I PepGen Inc. (Nasdaq: PEPG), a clinical-stage biotechnology company advancing the next generation of oligonucleotide therapies with the goal of transforming the treatment of severe neuromuscular and neurological diseases, today announced that the UK Medicines & Healthcare products Regulatory Agency (MHRA) has authorized its Clinical Trial Application (CTA) to initiate the CONNECT2-EDO51 Phase 2 clinical trial of PGN-EDO51 in patients with Duchenne muscular dystrophy (DMD) amenable to an exon 51-skipping approach.

“We are excited to take the next step forward in our development of PGN-EDO51, which we believe to be a potentially transformative investigational candidate for people living with DMD and are pleased the MHRA authorized our CTA. We believe this study, together with the data generated in our ongoing CONNECT1-EDO51 trial, could potentially support accelerated approval of EDO51, subject to alignment with regulators,” said James McArthur, Ph.D., President and CEO of PepGen. “We are grateful to continue our work with the DMD community to develop this therapy.”

The CONNECT2-EDO51 Phase 2 clinical trial is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study, that will enroll approximately 20 ambulatory and non-ambulatory boys and young men living with DMD amenable to exon 51-skipping, who are at least six years of age. Participants will receive seven doses of either PGN-EDO51 or placebo at approximately four-week intervals for 24 weeks. Per the protocol, the starting dose will escalate from 5 mg/kg to 10 mg/kg, and potentially higher; the same dose levels are being evaluated in the ongoing CONNECT1-EDO51 trial. Further dose escalation will be determined based on evaluation of safety data from prior dose cohort(s). Participants will provide a muscle biopsy at baseline and then at week 25. The trial will assess exon skipping, dystrophin production, and safety and tolerability. All participants will have the opportunity to participate in an open-label extension.

About PGN-EDO51

PGN-EDO51, PepGen’s lead clinical candidate for the treatment of DMD, utilizes the Company’s proprietary Enhanced Delivery Oligonucleotide (EDO) technology to deliver a therapeutic oligonucleotide that is designed to target the root cause of this devastating disease. PGN-EDO51 is designed to skip exon 51 of the dystrophin transcript, an established therapeutic target for approximately 13% of DMD patients, thereby aiming to restore the open reading frame and enabling the production of a truncated, yet functional dystrophin protein. In preclinical studies, PepGen observed that treatment of non-human primates with PGN-EDO51 resulted in greater levels of exon 51 skipping when compared in head-to-head studies against a molecule that we believe is structurally equivalent to the most clinically advanced peptide-conjugated oligonucleotide therapeutic candidate, which we believe could translate to higher levels of dystrophin production in patients. PGN-EDO51 also exhibited the highest level of exon 51 skipping in primate skeletal muscles, including the diaphragm, reported for any approved therapeutic or known development candidate at tolerable target dose levels, based on cross-trial comparisons of publicly available data. In humans, in a Phase 1 single ascending dose study in healthy volunteers, PGN-EDO51 also exhibited six times higher mean exon 51 skipping as compared to a naked oligonucleotide following a single dose, based on cross-trial comparisons of publicly available data.

About Duchenne Muscular Dystrophy (DMD)

Duchenne muscular dystrophy (DMD) is an X-linked recessive, progressive, muscle-wasting disease that predominantly affects boys. This debilitating disease is caused by genetic mutations in the gene encoding dystrophin, a protein necessary for normal muscle function, and is one of the most prevalent rare genetic diseases, with an incidence rate of approximately one in every 3,500 to 5,000 male births. DMD is characterized by progressive muscle weakness, which leads to patients losing the ability to walk, a loss of upper body function, cardiac issues and difficulties breathing. DMD is invariably fatal by young adulthood. Despite significant advances in treatments for this devastating disease, current exon skipping therapies are limited by poor delivery to muscle tissue and have yet to establish meaningful clinical benefit for DMD patients.

About PepGen

PepGen Inc. is a clinical-stage biotechnology company advancing the next-generation of oligonucleotide therapies with the goal of transforming the treatment of severe neuromuscular and neurological diseases. PepGen’s Enhanced Delivery Oligonucleotide, or EDO, platform is founded on over a decade of research and development and leverages cell-penetrating peptides to improve the uptake and activity of conjugated oligonucleotide therapeutics. Using these EDO peptides, we are generating a pipeline of oligonucleotide therapeutic candidates that are designed to target the root cause of serious diseases.