PepGen (PEPG) Leerink Global Healthcare Conference 2026 summary

Recent clinical progress and study updates

• Reported single-dose splicing improvements in DM1 patients: 12% at 5 mg/kg, 29% at 10 mg/kg, and 54% at 15 mg/kg, representing the highest levels seen to date.

• Multiple ascending dose (MAD) study, Freedom 2, is ongoing in several countries; 5 mg/kg cohort fully enrolled, with data expected by end of month.

• 10 mg/kg cohort is half enrolled, with four of eight patients dosed; 12.5 mg/kg cohort to start later this year and read out next year.

• Open-label extension trial is enrolling, with eight patients currently participating and no dropouts reported.

• The year is described as catalyst-rich, with significant data readouts expected to demonstrate best-in-class potential.

Regulatory and safety considerations

• FDA placed PGN-EDODM1 on partial clinical hold due to mouse toxicology findings, though these were not observed in non-human primates or patients.

• The company is preparing a complete response to the FDA, which will have 30 days to reply; efforts are focused on clarifying the relevance of preclinical data.

• Safety data from the 5 mg/kg and 10 mg/kg cohorts show no kidney or electrolyte-related adverse events; transient effects at higher doses resolved quickly.

• Dose escalation decisions are guided by DSMB reviews and ongoing safety monitoring, with 12.5 mg/kg set as the top dose due to observed DLT at 15 mg/kg.

Efficacy expectations and biomarker strategy

• Aims to achieve mid-teen splicing improvements at 5 mg/kg and 30%+ at 10 mg/kg in multi-dose settings, building on strong single-dose results.

• Splicing correction is considered a key pharmacodynamic marker, but not yet accepted by regulators as a surrogate for accelerated approval.

• Functional outcomes, including vHOT and Five Times Sit to Stand, are being evaluated, with trial design adjustments to reduce variability.

• The approach targets CUG repeats, differentiating from DMPK knockdown strategies and offering potential safety and efficacy advantages.

• Open-label extension and MAD cohorts will further inform dose selection and support potential phase III advancement.