PepGen Raises $45 Million to Advance Oligonucleotide Platform Targeting Rare Neuromuscular and Cardiac Diseases

Rare Daily Staff

PepGen closed a $45 million of series A funding to advance its oligonucleotide platform targeting rare neuromuscular and cardiac diseases, including Duchenne muscular dystrophy.

RA Capital Management led the financing with participation from Oxford Sciences Innovation, the company’s original seed investor, the University of Oxford, and CureDuchenne Ventures.

PepGen will use the funding to advance into the clinic their next-generation cell-penetrating peptides conjugated to phosphorodiamidate morpholino oligomers (PPMOs) that are designed to correct genetic defects in diseases with high unmet medical need. PepGen says its proprietary PPMO technology will dramatically enhance delivery of oligonucleotides to key tissues, while also improving safety compared with competing therapies.

“PepGen’s cell-penetrating peptide (CPP) technology represents an important step change in that we have succeeded in optimizing cellular uptake whilst simultaneously engineering out the safety signals that historically impacted earlier attempts at this approach,” said PepGen co-founder Matthew Wood, professor of neuroscience at the University of Oxford.

PepGen’s lead indications include Duchenne muscular dystrophy (DMD), a rare, lethal, inherited neuromuscular disease that occurs in approximately one in every 3,500 to 5,000 male births globally. It is caused by a mutation in the gene that encodes instructions for dystrophin, a key structural protein. Symptoms of DMD usually appear in infants and toddlers. Affected children may experience developmental delays such as difficulty in walking, climbing stairs or standing from a sitting position. As DMD progresses, muscle weakness in the lower extremities spreads to the arms, neck and other areas. Most patients require full-time use of a wheelchair in their early teens, and then progressively lose the ability to independently perform activities of daily living. Eventually, patients have difficulty in breathing due to respiratory muscle dysfunction, which ultimately may require ventilator support. Cardiac muscle dysfunction frequently leads to heart failure and death. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

“Patients born with Duchenne muscular dystrophy lack dystrophin, a critical protein that confers structural integrity on muscle,” said Caroline Godfrey, CEO and co-founder of PepGen. “PepGen is developing unique, proprietary cell-penetrating peptides that we expect will improve upon the efficacy of existing exon-skipping approaches to restore dystrophin expression in DMD patients.”

A key benefit of PepGen’s platform is its unique potential to reach all the tissues affected by DMD and other inherited neuromuscular and cardiovascular conditions. Notably, unlike other approaches, PepGen’s drug candidates strongly distribute to cardiac tissue. Heart disease is a key cause of morbidity and mortality in these devastating conditions.

“With the recent approvals of treatments that generate small increases in dystrophin in skeletal muscle, patients may be ambulating and living longer, but this in turn is expected to shift the burden of morbidity and mortality towards an epidemic of heart disease, which is not adequately addressed by current DMD therapies,” said Ramin Farzaneh-Far, venture partner at RA Capital Management, PepGen’ executive chair, and a board-certified cardiologist.

“PepGen, we believe, represents a potential breakthrough approach for which DMD patients and their caregivers have been hoping against hope, said Debra Miller, CEO of CureDuchenne Ventures. “Virtually all Duchenne patients have cardiomyopathy, and cardiac failure is prevalent amongst this population, so therapies addressing this unmet need promise a major impact for the Duchenne community.”

In addition to DMD, PepGen has a pipeline of drugs targeting rare neuromuscular and neurologic diseases, with a particular focus on those with severe cardiac manifestations as well as primary cardiac conditions.

PepGen’s cell-penetrating peptide technology for oligonucleotide delivery was developed over more than a decade of research in the UK, and arose from collaborations between the neuroscience laboratory of Matthew Wood at the University of Oxford and the peptide chemistry laboratory of Mike Gait at the MRC Laboratory of Molecular Biology in Cambridge.

PepGen was spun out in 2018 with a seed investment of $6 million (£4.5 million) from OSI to commercialize the cell-penetrating peptide platform. The company received additional support from Innovate UK, the UK’s innovation agency.

PepGen’s new corporate headquarters will be in Boston, and its research hub will continue in the United Kingdom.

Photo: Caroline Godfrey, CEO and co-founder of PepGen