PepGen has shared positive initial data from its ongoing FREEDOM-DM1 Phase I trial, which is evaluating PGN-EDODM1 in patients with myotonic dystrophy type 1 (DM1).
In the 5mg/kg and 10mg/kg dose cohorts of the trial, participants showed a mean splicing correction of 12.3% and 29.1%, respectively.
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These results were measured by a 22-gene panel 28 days after dosing.
A dose-dependent increase in muscle tissue concentrations of PGN-EDODM1 was also noted on day 28.
Although single-dose studies have not yet shown functional improvements in individuals with DM1, PepGen gathered these cohorts’ data that indicates positive early trends in some functional outcome measures.
PepGen anticipates that repeated dosing and splicing correction with PGN-EDODM1 could lead to significant ‘functional improvements’ over time.
The therapy has shown a “favourable” emerging safety profile in both the 5mg/kg and 10mg/kg cohorts up to the data cut-off date of 3 December 2024.
PepGen expects to share outcomes from the 15mg/kg cohort of the FREEDOM trial in the second half of this year and the 5mg/kg cohort of the FREEDOM2 trial in the first quarter of 2026.
PepGen president and CEO James McArthur said: “We believe these results provide initial validation of PGN-EDODM1’s ability to selectively bind the pathogenic CUG-repeat DMPK RNA, and we look forward to evaluating PGN-EDODM1 with more doses over longer periods in our FREEDOM2-DM1 multiple ascending dose study.
“Based on these initial results, we aim to build on the significant correction of mis-splicing observed in this single-dose study to potentially provide improved functional benefit for patients who currently have no available approved therapeutic options.”
PGN-EDODM1, which leverages the EDO technology of the company, is designed for restoring the normal splicing function of MBNL1, a crucial RNA splicing protein, the company stated.
DM1 is a monogenic and autosomal dominant disorder that impairs cardiac, skeletal, as well as smooth muscles and can also affect the central nervous system.
