Science
Empowering oligonucleotide therapeutics
Our Unique Approach
We are advancing the next generation of oligonucleotide therapeutics with the goal of transforming the treatment of severe neuromuscular and neurological diseases. Our Enhanced Delivery Oligonucleotide (EDO) platform leverages cell-penetrating peptide conjugates to improve the activity and tolerability of oligonucleotide cargo therapeutics.
Peptides are molecules made of linked amino acids; they are commonly found in nature and play many roles in the body. Our innovative, proprietary EDO peptides are engineered for optimal tissue and cell penetration, and they have demonstrated the ability to transport oligonucleotides into a broad range of target tissues, including smooth, skeletal and cardiac muscle, and the CNS.
Using our EDO peptides, we are generating a pipeline of oligonucleotide therapies that target the root cause of serious neuromuscular diseases. Our mission is to deliver transformative therapeutics to those in need and our innovative technology is well-positioned to effect this change for patients, families and the broader healthcare community.
The Challenge
Oligonucleotide therapeutics are a genetic medicine modality that can target the root cause of many diseases through the modulation of RNA expression and processing. However, despite the considerable potential of these therapies, the development of oligonucleotide therapeutics has been limited by challenges in their delivery. On their own, oligonucleotide therapeutics are not readily distributed to heart and skeletal muscle, the key affected tissues in neuromuscular diseases like Duchenne muscular dystrophy (DMD), and myotonic dystrophy type 1 (DM1) and are not efficiently taken up into these cells.
PepGen’s Solution: Our Enhanced Delivery Oligonucleotide Platform
To address this challenge, we engineered our proprietary EDO technology to optimize tissue and cell penetration, which we believe may result in the enhanced therapeutic activity and improved tolerability of oligonucleotide therapies. Our platform is based on novel cell-penetrating EDO peptides that were developed through an iterative process that selected simultaneously for high uptake; biodistribution to key muscle targets, including cardiac tissue; and improved tolerability.
Our lead product candidates in DMD and DM1 utilize one of these optimized, proprietary, novel EDO peptides, and we are continuing to build and develop this platform technology as we expand into new therapeutic areas.
PEPGEN’S enhanced DELIVERY PEPTIDES
- Next-generation delivery peptides
- Engineered with the goal of offering enhanced tolerability & activity
THERAPEUTIC OLIGONUCLEOTIDES
- Precision medicines that target the root cause of disease
- Limited by delivery challenges
ENHANCED DELIVERY OLIGONUCLEOTIDES
- Drive efficient cellular uptake of oligonucleotides, including in smooth, skeletal and cardiac muscle tissue and in the CNS
- A modular platform that supports rapid pipeline expansion
Publications
Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice
Klein et. al., The Journal of Clinical Investigation (2019), online publication ahead of print version
Cell-Penetrating Peptide Conjugates of Steric Blocking Oligonucleotides as Therapeutics for Neuromuscular Diseases from a Historical Perspective to Current Prospects of Treatment
Gait et. al., Nucleic Acid Therapeutics (2018), 29(1), 1
How much dystrophin is enough: the physiological consequences of different levels of dystrophin in the mdx mouse
Godfrey et. al., Human Molecular Genetics (2015), 24(15), 4225
Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment
Betts et. al., Molecular Therapy–Nucleic Acids (2012, 1(8), e38
Targeting RNA to treat neuromuscular disease
Muntoni and Woods, Nature Reviews Drug Discovery (2011), 10, 612