P.120 Unlocking the potential of oligonucleotide therapeutics for Duchenne muscular dystrophy through enhanced delivery

PGN-EDO51 is PepGen's clinical candidate to treat individuals with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. It is the first of a series of therapies based on our Enhanced Delivery Oligonucleotide (EDO) platform and will be followed by programs to address myotonic dystrophy type one, other subgroups of DMD and other neuromuscular and neurological disorders. Therapeutic oligonucleotides are precision medicines that modulate the genetic machinery and have shown great promise in treating genetic disorders. First generation oligonucleotides resulted in suboptimal delivery to muscle and therefore afford limited dystrophin production and limited therapeutic benefit in people with DMD. PepGen's EDO technology efficiently and effectively delivers oligonucleotides to skeletal, smooth and cardiac muscle, offering great promise for neuromuscular diseases. Studies in the mdx mouse model of DMD demonstrated robust dystrophin production in key tissues following a single administration, inducing 91% of normal levels in quadriceps seven days after dosing. Single dose studies in non-human primates (NHPs) established that PGN-EDO51 leads to robust exon skipping in muscle and drives broad biodistribution, with significant levels detected in skeletal, smooth and cardiac muscles and in CNS tissues. Repeat dose studies in NHPs demonstrated that exon skipping levels accumulate. Following three doses of 30 mg/kg, exon skipping levels of 78% in biceps, 76% in diaphragm and 24% in left ventricle were obtained. PGN-EDO51 was well tolerated at target doses, and clinical trials enabling toxicology studies have been completed. The high levels of activity and the tolerability of our approach demonstrated by the totality of studies supported our Clinical Trial Application to Health Canada and the initiation of our Phase 1 clinical trial in early 2022. Results from this Phase 1 safety study in healthy volunteers and plans for our Phase 2 studies will be discussed.