PepGen today shared data from its Phase I trial of PGN-EDO51 in healthy volunteers. PGN-EDO51 is an PMO-exon skipping therapy bound to a peptide which improves uptake into muscle cells, and targets those amenable to exon 51 skipping.

Based on these results, PepGen plans to initiate a Phase 2a clinical trial in participants with Duchenne amenable to exon 51 skipping in the first half of 2023. PepGen will also report out data on its earlier stage candidates for skipping exons 53, 45 and 44 over the next months.

We look forward to continued updates from PepGen as the program advances.

Read the Community Letter from PepGen

Dear Duchenne Community:

PepGen is pleased to announce data from our Phase I trial of PGN-EDO51 in healthy volunteers. PGN-EDO51 is our clinical candidate for the treatment of Duchenne amenable to exon 51 skipping (https://investors.pepgen.com/news-releases/news-release-details/pepgen-reports-positive-data-phase-1-trial-pgn-edo51-treatment). It is the first of a series of “enhanced delivery oligonucleotides” (EDOs) that are being investigated for a number of indications, including Duchenne amenable to the skipping of other exons.

PepGen’s Phase 1 study of PGN-EDO51 was a single ascending dose clinical trial evaluating the safety and tolerability of PGN-EDO51 in 32 healthy adult males. It found that:

• PGN-EDO51 exhibited the highest levels of oligonucleotide delivery to muscle that have been reported in single-dose human studies to date.
• PGN-EDO51 exhibited the highest levels of exon skipping that have been reported in single-dose human studies to date.
• PGN-EDO51 was generally well tolerated.

The persistence of the oligonucleotide in biceps, coupled with the observed increased exon skipping from Day 10 to Day 28, supports the idea that we will see accumulation of exon skipped transcript and dystrophin in DMD patients following multiple doses.

Based on these exciting results, PepGen is planning on initiating a multiple ascending dose clinical trial in people with DMD amenable to exon 51 skipping in the first half of 2023. We will also report out data on our earlier stage candidates for skipping exons 53, 45 and 44 over the next months.

We are very grateful to the Duchenne community, which has worked closely with us as we are designing our clinical programs. We look forward to sharing more information with you about these results and those from our other Duchenne programs, as well as further information about our upcoming trial over the next months.

Thank you,

Jane, Alayna and the PepGen team

Read the Press Release from PepGen

PepGen Reports Positive Data from Phase 1 Trial of PGN-EDO51 for the Treatment of Duchenne Muscular Dystrophy

September 28, 2022

– PGN-EDO51 exhibited the highest levels of oligonucleotide delivery and exon skipping in a clinical study following a single dose when compared to publicly available clinical data for other exon 51 skipping approaches –

– PGN-EDO51 was generally well-tolerated –

– PepGen plans to initiate a Phase 2a multiple ascending dose (MAD) clinical trial in Duchenne muscular dystrophy (DMD) patients in 1H 2023 –

– Data supports the potential of PepGen’s Enhanced Delivery Oligonucleotide (EDO) platform in neuromuscular diseases –

– Company to host conference call today at 8:00 a.m. ET to discuss these results –

BOSTON, Sept. 28, 2022 (GLOBE NEWSWIRE) — 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 results from its completed Phase 1 healthy normal volunteer (HNV) trial of PGN-EDO51, the company’s lead product candidate for the treatment of DMD patients whose mutations are amenable to an exon 51 skipping approach.

PepGen’s Phase 1 HNV trial of PGN-EDO51 was a single ascending dose (SAD) clinical trial evaluating the safety and tolerability of PGN-EDO51 in 32 healthy adult males. Oligonucleotide tissue concentration and exon skipping were also assessed. Following intravenous administration of PGN-EDO51, safety data were evaluated by a Safety Review Committee prior to progressing to the next dose level. Volunteers were dosed with either 1, 5, 10 or 15 mg/kg of PGN-EDO51 or placebo. The trial met its primary endpoint assessing the safety profile of PGN-EDO51 at pharmacologically relevant doses.

“We are thrilled to announce that we have observed very high levels of oligonucleotide delivery and exon skipping in muscle in our Phase 1 HNV trial. The EDO technology performed above our expectations,” said James McArthur, Ph.D., President and CEO of PepGen. “In biopsies taken from biceps, PGN-EDO51 exhibited mean exon 51 skipping levels of 1.4% following a single dose of 10 mg/kg, and mean levels of 2.0% following a single dose of 15 mg/kg. Based on cross-trial comparisons with publicly available data, we believe that these results are unprecedented and reflect the highest level of DMD exon 51 skipping observed in a clinical trial following a single dose. With the very encouraging outcome of this trial, PepGen plans to initiate a Phase 2a multiple ascending dose clinical trial in DMD patients in the first half of 2023. We extend our heartfelt appreciation to the participants in our Phase 1 HNV trial for their role in supporting our mission to develop transformative therapies for people living with DMD and other devastating neuromuscular diseases.”

Dr. McArthur added: “We are particularly pleased with the high levels of exon skipping observed for PGN-EDO51 at 28 days. Exon skipping was higher on Day 28 than at Day 10, which we believe, in conjunction with our tissue concentration data, suggests both sustained drug exposure and pharmacodynamic effect. Furthermore, we believe that these results could signal the potential for the accumulation of exon 51 skipped transcript and dystrophin protein in muscle tissue with repeated doses of PGN-EDO51 in people living with DMD.”

Safety and Tolerability Data

The trial met its primary endpoint providing evidence that PGN-EDO51 was generally well tolerated at pharmacologically relevant doses.

• All participants completed the trial; there were no discontinuations.
• The majority of treatment-emergent adverse events (TEAEs) were assessed as mild and resolved without any intervention. At 10 mg/kg, there were only Grade 1 (mild) adverse events (AEs).
• At 15 mg/kg, there were mild, transient, reversible changes in kidney biomarkers that resolved without intervention in all but one HNV who received IV hydration. This event was recorded as a non-life-threatening serious adverse event (SAE).
• Transient mild (Grade 1) to moderate (Grade 2) hypomagnesemia was observed in two participants at the 15 mg/kg dose and did not require any intervention.
• Serum cystatin C, the recommended biomarker to assess renal function in DMD, showed minimal change at the highest dose.

Oligonucleotide Tissue Concentration and Exon Skipping Results

A dose dependent increase in PGN-EDO51 tissue concentration and exon skipping was observed in biceps.

• Oligonucleotide Tissue Concentration:
  • In the 10 mg/kg dose cohort, PGN-EDO51 exhibited mean oligonucleotide tissue concentrations of 19 nM and 11 nM in biceps biopsies taken at Day 10 (n=6) and Day 28 (n=6), respectively.
  • In the 15 mg/kg dose cohort, PGN-EDO51 exhibited mean oligonucleotide tissue concentrations of 50 nM and 50 nM in biceps biopsies taken at Day 10 (n=5) and Day 28 (n=6), respectively.
• Exon skipping:
  • In the 10 mg/kg dose cohort, PGN-EDO51 exhibited mean exon skipping of 1.1% and 1.4% in biceps biopsies taken at Day 10 (n=6) and Day 28 (n=6), respectively.
  • In the 15 mg/kg dose cohort, PGN-EDO51 exhibited mean exon skipping of 1.4% and 2.0% in biceps biopsies taken at Day 10 (n=5) and Day 28 (n=6), respectively.

PepGen believes that these data could indicate the potential for clinically meaningful accumulation of exon 51-skipped transcripts and dystrophin in tissue with repeated doses of PGN-EDO51.

PepGen plans to present the full results from the Phase 1 HNV trial of PGN-EDO51 at an upcoming medical meeting, and the company remains on track to initiate a planned Phase 2a MAD trial evaluating PGN-EDO51 in DMD patients in the first half of 2023.

Implications for PepGen’s Myotonic Dystrophy Type 1 (DM1) program and EDO pipeline

We believe that these data also support the potential of PGN-EDODM1, PepGen’s lead product candidate for the treatment of DM1, and our pipeline of EDO therapeutic candidates. The tissue concentrations observed in the Phase 1 HNV trial of PGN-EDO51 were similar to those seen in a single-dose study of PGN-EDODM1 conducted in HSA^LR mice, a murine model of DM1, at pharmacologically active dose levels. These tissue concentrations of PGN-EDODM1 resulted in significant correction of mis-splicing and myotonia in this mouse model of disease. Dr McArthur said, “We are encouraged by these results, which we believe support the potential of PGN-EDODM1 to treat the root cause of DM1 and drive meaningful clinical outcomes for individuals living with this disease. In addition, we are committed to the DMD community, with EDO candidates for patients amenable to an exon 53, 45 and 44 approach currently in development. We believe that these results provide robust support for the potential of these candidates to change the course of disease for those living with DMD.”

Read the full release.