PepGen (PEPG) investor relations material

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.

• 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 patient benefit.

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

Mechanism of action and functional endpoints

• EDO technology enables efficient nuclear delivery, achieving up to 100-fold higher levels than naked oligos.

• The therapeutic targets pathogenic CUG repeats, reducing foci and correcting mis-splicing in both animal models and patients.

• VHOT is used as an early indicator, with baseline variability managed through improved screening and measurement.

• Hand strength and ankle dorsiflexion are also tracked as functional endpoints, with splicing improvement expected to translate to functional benefit.

• Aiming for endpoints that are reliable and approvable, with openness to non-VHOT measures for registration.

Safety profile and regulatory considerations

• No treatment-emergent kidney adverse events 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 28-day intervals does not indicate concerning renal accumulation.

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

• 10 mg/kg is considered safe and may be the target dose, with higher doses explored for regulatory engagement.