PepGen (PEPG) Study update summary

Study design and dosing/objectives

• FREEDOM2 is a phase II, multiple ascending dose study in DM1, with three cohorts and four monthly doses per patient, randomized 3:1 or 6:2 active to placebo, escalating up to 12.5 mg/kg.

• The 5 mg/kg cohort included eight patients, with ongoing enrollment in the 10 mg/kg cohort and results expected in H2 2026.

• Key endpoints are safety, splicing correction, and functional outcomes.

• PGN-EDODM1 uses proprietary EDO technology to restore normal splicing of MBNL1 by targeting CUG repeat expansions in DMPK transcripts.

• PGN-EDODM1 has received Orphan Drug and Fast Track designations from the FDA and Orphan Designation from the EMA.

Safety and tolerability/results

• At 5 mg/kg, all adverse events were mild or moderate, with no serious or kidney-related events, no cumulative toxicity, and no treatment-related discontinuations.

• Nausea was the most common adverse event; transient albuminuria occurred in two subjects but resolved without intervention.

• No hypomagnesemia, hypersensitivity, or renal function issues were observed.

• Safety profile supports dose escalation to 10 mg/kg and potentially 12.5 mg/kg.

Efficacy and biomarker data/results

• Mean splicing correction in the 5 mg/kg group was 7.3% versus 6.8% in placebo; excluding one outlier, mean correction rose to 22.9%.

• One treatment patient showed a 70.8% worsening in splicing, considered a rare outlier event.

• High muscle concentrations of EDODM1 (mean 158 ng/g) were observed in treated patients.

• vHOT improved up to 4.1 seconds through week 13 in the treatment group, returning to baseline by week 16; excluding the outlier, vHOT improved up to three seconds at all time points through week 16.

• No meaningful improvements in 10-meter walk/run test or handgrip strength at 5 mg/kg.