PepGen (PEPG) Virtual CNS Forum summary

Key clinical program updates

• Achieved 29% splicing correction at 10 mg/kg in DM1 single-dose study, surpassing other approaches; 15 mg/kg data expected later this year.

• Early data show improved 10-meter walk/run in DM1, with all adverse events mild and no serious treatment-related events.

• DMD program to report 10 mg/kg dystrophin data this summer; prior data showed higher exon 51 skip transcript at lower doses than competitors.

• Multiple ascending dose (MAD) study in DM1 to begin with 5 mg/kg cohort, with data expected early next year; 10 mg/kg MAD timing to be updated later.

• CONNECT2 DMD study paused until CONNECT1-EDO51 data readout to inform next steps.

Data interpretation and methodology

• Robust dose response in DM1: 12% splicing correction at 5 mg/kg, 29% at 10 mg/kg, using industry-standard gene panels.

• Variability in vHOT outcome attributed to patient selection; future studies will refine baseline criteria for more reliable results.

• At 10 mg/kg, lowest splicing correction observed was 17%; two patients excluded from analysis due to non-evaluable samples.

• Splicing correction is considered a key biomarker, but FDA approval will require demonstration of clinical benefit in functional and patient-reported outcomes.

Safety and tolerability

• DM1 drug EDO-DM1 shows a better safety profile than DMD drug EDO-51, with no movement in kidney biomarkers at 10 mg/kg.

• DMD drug EDO-51 showed transient increases in kidney biomarkers at higher doses, but all adverse events were reversible and mild.

• Non-human primate studies support better safety for DM1 candidate; differences may relate to oligo size and kidney clearance.