PepGen Inc. announced results from its completed Phase 1 healthy normal volunteer 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 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.

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 were assessed as mild and resolved without any intervention.

At 10 mg/kg, there were only Grade 1 adverse events. 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.

Transient mild to moderate 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. 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.