PepGen (PEPG) Stifel 2025 Healthcare Conference summary

Clinical trial progress and efficacy results

• Achieved over 50% splicing improvement at 15 mg/kg in DM1 patients, surpassing previous benchmarks for the disease.

• Single-dose data showed 12% and 29% splicing improvement at 5 and 10 mg/kg, respectively.

• Upcoming multiple ascending dose (MAD) study will report 5 mg/kg data in Q1 next year, aiming to build on single-dose results.

• Functional outcome measures have been refined to better demonstrate clinical benefit.

• Expansion into new geographies is planned to accelerate cohort enrollment.

Mechanism of action and functional endpoints

• EDO technology enables efficient nuclear delivery, resulting in higher splicing correction compared to other approaches.

• Targeting pathogenic CUG repeats leads to reduction in foci and correction of mis-splicing in both animal models and patients.

• Functional endpoints include VHOT, hand strength, ankle dorsiflexion, and 10-meter walk-run, with splicing improvement expected to translate into functional gains.

• VHOT is highly variable; baseline requirements and measurement frequency have been adjusted to reduce variability.

• Aim to demonstrate benefit in non-VHOT measures for broader patient impact.

Safety profile and regulatory considerations

• No treatment-emergent kidney adverse events observed at 5 or 10 mg/kg in DM1 single-dose studies.

• Renal biomarker changes in DMD were mild, transient, and reversible; DM1 shows a larger therapeutic window.

• Repeat dosing at day 28 does not indicate concerning renal accumulation.

• FDA focus is on benefit-risk balance, with reversibility and transience of adverse events being key.

• Higher doses (10–15 mg/kg) will be explored for regulatory engagement and understanding, not due to safety concerns.