We are also advancing discovery programs in additional neuromuscular and neurological indications to continue to leverage the broad potential of PepGen’s Enhanced Delivery Oligonucleotide (EDO) technology.
Therapies with the
potential to halt disease
PepGen is advancing a pipeline of disease-modifying, peptide-conjugated oligonucleotide candidates to treat neuromuscular and neurological disorders, beginning with Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). These treatments have the potential to halt the progression of these disorders.
PepGen’s clinical candidates for DMD and DM1 have demonstrated early signs of activity as well as being generally well tolerated, and we are focused on continuing to advance these therapies through clinical trials.
PGN-EDO51 targets exon 51, a validated genetic target in approximately 13 % of DMD patients. By blocking the inclusion of exon 51, the proper dystrophin-producing reading frame is restored, and a shortened, but functional, dystrophin is produced.
In clinical and preclinical studies to date, PGN-EDO51 has demonstrated:
- The highest levels of oligo delivery & exon 51 skipping in humans following a single dose*
- The highest level of exon 51 skipping in NHP skeletal muscle at tolerable target dose levels, and highest level of dystrophin production in mdx mouse skeletal muscle**
- Generally well tolerated
We are also advancing additional candidates targeting additional validated genetic targets including Exon 53, Exon 45, and Exon 44.
* Comparative statements are based on cross-trial comparisons with publicly-available data for other exon skipping approaches that have been assessed following a single dose in humans, and following single and multiple doses in NHP.
** Of clinical-stage DMD therapies.
PGN-EDODM1 was designed to liberate MBNL1 from toxic DMPK-CUG expansion foci without degrading DMPK. DM1 is caused by CUG repeats that form hairpin loops in the DMPK RNA that cause sequestering of the MBNL1 protein, a key RNA processing factor protein. This results in downstream mis-splicing events and aberrant expression of myotonic dystrophy protein kinase, a protein that plays a critical role in muscle contraction and relaxation. By blocking the toxic CUG repeats, functional downstream splicing and muscle function are restored.
In preclinical studies to date, PGN-EDODM1 has demonstrated:
- Broad biodistribution and delivery to key tissue types
- Achievement of greater than 60% correction of the mis-splicing events in a murine model of DM1, resulting in a complete reversal of myotonia
- Sustained correction of mRNA mis-splicing for up to six months following a single dose
- Generally well tolerated