CONNECT1-EDO51: A 12-Week Open-Label Phase 2 Study to Evaluate PGN-EDO51 Safety and Efficacy in People with Duchenne Amenable to Exon 51 Skipping

Topic:

Clinical Trials

Poster Number: O74

Author(s):

Bassem Morcos, MD, PepGen Inc. MA, USA, Hugh McMillan, MD, Children's Hospital of Eastern Ontario, Ottawa, Canada, Nicolas Chrestian, MD, FRCPC, CSCN, CHU De Quebec-Universite Laval QC, Canada, Hernan D. Gonorazky, MD, CSCN, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, Jane Larkindale, PhD, PepGen, Sarah Vacca, BS, PepGen Inc. MA, USA, Mark Peterson, PepGen Inc. MA, USA, Pallavi Lonkar, Ph.D., PepGen, Brijesh Garg, PhD, PepGen, Shaoxia Yu, PhD, PepGen, Patricia Fraser, MD, MPH, MS, PepGen Inc. MA, USA, Sejal Batra, MS, PepGen Inc. MA, USA, Gregory Song, PhD, MBA, PepGen Inc. MA, USA, Michelle Mellion, MD, PepGen Inc. MA, USA

BACKGROUND: PepGen’s enhanced delivery oligonucleotide (EDO) cell-penetrating peptide technology is engineered to optimize tissue delivery and cellular uptake of oligonucleotides. PGN-EDO51 is PepGen’s investigational candidate for the treatment of Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. The program includes two Phase 2 multiple ascending dose (MAD) studies: CONNECT1-EDO51, an open-label study conducted in Canada (NCT06079736), and CONNECT2-EDO51, a multinational randomized double-blind placebo-controlled study. Participants who complete the MAD period in either study may continue dosing in a long-term extension (LTE).
OBJECTIVE: CONNECT1-EDO51 study objective is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics (dystrophin and exon skipping) of PGN-EDO51 following repeat dosing.
METHODS: Main inclusion criteria are age ≥8 years with confirmed genetic diagnosis of DMD amenable to exon 51 skipping, and weight ≥25 kg. Participants will receive PGN-EDO51 in ascending doses across 3 cohorts. All participants (N=11) will receive 4 doses of PGN-EDO51 at approximately 4-week intervals over 12 weeks. Muscle biopsies are taken at Baseline and Week 13. Protocol amendment pending regulatory review.
RESULTS: The first cohort (n=3) received repeat doses of 5 mg/kg. PGN-EDO51 was well tolerated with mild adverse events. 1 participant had 2 related nonserious TEAEs. There were no serious adverse events, nor sustained elevation in kidney biomarkers, hypomagnesemia, hypokalemia, anemia, thrombocytopenia, dose discontinuations, interruptions or modifications.
All participants demonstrated increases in exon skipping and dystrophin production. PGN-EDO51 resulted in 2.15% mean exon skipping and mean dystrophin of 0.61% (unadjusted) and 1.49% (adjusted for muscle content); increases from baseline of 0.26% and 0.70%, respectively. All participants continue dosing in the LTE.
Dosing in the 10 mg/kg cohort is ongoing.
CONCLUSION: These results, after 3 months and 4 doses of 5 mg/kg, are encouraging. Potentially higher dystrophin production is expected with higher doses of PGN-EDO51 over longer treatment periods, which will be assessed in CONNECT2.