PepGen (PEPG) Leerink’s Global Healthcare Conference 2025 summary

Key clinical program updates

• Myotonic Dystrophy Type 1 program showed 12% and 29% correction of missplicing at 5 mg/kg and 10 mg/kg, respectively, after a single dose, surpassing expectations and previous studies.

• Multiple ascending dose studies are ongoing, with higher doses and longer-term therapy expected to further improve efficacy and safety outcomes.

• DMD program is advancing, with upcoming data from the 10 mg/kg cohort expected to show higher dystrophin production.

• CONNECT1 study in DMD is fully enrolled, with data readout expected in the early second half of the year; CONNECT2 enrollment paused pending CONNECT1 results.

• Safety profile in DM1 is favorable, with no kidney modulation observed at current doses; DMD patients show manageable, reversible hypomagnesemia.

Platform technology and mechanistic insights

• EDO technology enables high nuclear delivery of oligonucleotides, critical for targeting nuclear toxic foci in DM1 and DMD.

• EDO conjugation allows oligos to exit the endosome efficiently, increasing access to the nucleus and enhancing therapeutic effect.

• High levels of nuclear delivery and splicing correction have been demonstrated in cells, non-human primates, and healthy volunteers.

• The differentiated safety profile in DM1 is attributed to a smaller oligo and different GC content compared to DMD.

• The platform shows potential for best-in-class drugs across multiple diseases, with additional applications in the research pipeline.

Clinical development strategy and future plans

• Multiple baseline evaluations are being implemented to reduce variability in outcome measures like vHOT.

• Next data readouts: 15 mg/kg single ascending dose in DM1 in the second half of the year, multi-dose data early next year.

• Phase 3 planning will focus on reliable, predictable endpoints, with functional benefits assessed at three months.

• Dose escalation up to 20 mg/kg is being considered in both SAD and MAD studies.

• Patient-reported outcomes and functional measures, including neurological and quality-of-life aspects, are being captured.