Creating the New Generation of Genetic Therapies

PepGen’s Enhanced Delivery Oligonucleotide Platform

Pipeline

We are currently advancing a pipeline of EDO candidates to treat a variety of degenerative neuromuscular diseases, including Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). Given our enhanced ability to reach targeted tissues effectively and safely, we believe our candidates may have significant advantages over currently marketed therapies and others in development.

What are Enhanced Delivery Oligonucleotides?

Peptides are molecules that consist of a series of amino acids linked together. They are commonly found in nature and play many roles in the body. PepGen’s novel Enhanced Delivery Peptides are the core of the company’s technology– they are innovative and unique and have proven to be highly effective delivery agents for therapeutic cargos such as oligonucleotides.

Oligonucleotides are short strings of nucleotides – adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U) – the building blocks that make up our DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). Linking specific sequences of these nucleotides together enables the creation of biomolecules that employ a variety of mechanisms to target a broad array of diseases of genetic origin as well as pathogens like viruses and bacteria.

There are many types of oligo chemistries that can be used to make synthetic oligos. PepGen is developing phosphorodiamidate morpholino oligonucleotides (PMOs), which are very stable, charge-neutral nucleic acids where the five-membered ribose heterocycle is replaced by a six-membered morpholine ring, helping to stabilize the molecule and improve in vivo safety.

We create our Enhanced Delivery Oligonucleotide (EDO) candidates by chemically linking our proprietary Enhanced Delivery Peptides to our therapeutic synthetic oligonucleotide to create EDOs to treat diseases.

Relevant 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