PepGen (PEPG) Corporate Presentation summary

Technology platform and clinical rationale

• EDO platform enables up to 25x higher nuclear uptake of oligonucleotides, addressing delivery limitations in muscle cells for neuromuscular diseases.

• The platform underpins a pipeline for serious genetic neuromuscular and neurological disorders, including myotonic dystrophy type 1.

• EDO51 targets the root cause of DMD by increasing exon 51 skipping and dystrophin production, with EDO51 and EDO53 programs potentially addressing 21% of DMD patients.

• Preclinical studies showed dramatic increases in oligonucleotide uptake and nuclear delivery compared to naked oligonucleotides.

• The platform is being expanded to additional DMD exon skipping candidates and other neuromuscular/neurological disease programs.

Clinical program overview and trial design

• CONNECT-1 is an open-label, multiple ascending dose trial in DMD patients aged 8+, evaluating safety, tolerability, dystrophin, muscle tissue concentration, and exon skipping.

• Both ambulatory and non-ambulatory patients are included, with doses of 5 mg/kg and 10 mg/kg; safety is reviewed by a Data Safety and Monitoring Board before escalation.

• All patients in the 5 mg/kg cohort continued into a long-term extension study.

• CONNECT-2, a phase II trial, is open in the UK and will open in the US by year-end, designed to support accelerated approval.

• DMD affects ~40,000 patients in the US and EU, with ~21% amenable to exon 51 skipping.

Efficacy and safety results (5 mg/kg cohort)

• EDO51/PGN-EDO51 at 5 mg/kg was well tolerated, with only mild, transient adverse events and no discontinuations or serious adverse events.

• Achieved mean exon 51 skipping of 2.15% after 3 months, the highest reported at this dose and duration compared to other therapies.

• Muscle content-adjusted dystrophin increased by 0.70% to 1.49%, and total dystrophin by 0.26%.

• EDO51/PGN-EDO51 outperformed DYNE-251 at the same dose and time frame in both exon skipping and dystrophin production, with 5-9 fold higher exon skipping efficiency per muscle PMO concentration.

• Exon skipping and dystrophin increases were achieved with fewer doses and shorter treatment periods than comparator therapies.