Rare Daily Staff

PepGen raised $112.5 million in a series B crossover financing round to advance its oligonucleotide platform targeting rare neuromuscular and cardiac diseases, including Duchenne muscular dystrophy.

Existing investors in the oversubscribed round included Ra Capital Management, Oxford Sciences Innovation, and CureDuchenne Ventures. New investors included Viking Global Investors, Deerfield Management Company, Adage Capital Management, Samsara Biocapital, Laurion Capital Management, Tudor Investment, Gray’s Creek Capital Partners, and other leading investors.

PepGen’s cell-penetrating peptide technology for oligonucleotide delivery was developed over more than a decade of research in the United Kingdom 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.

The technology uses 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.

In preclinical studies, PepGen has shown that its Enhanced Delivery Oligonucleotide (EDO) platform can deliver oligonucleotide candidates efficiently, safely, and reliably to skeletal, cardiac, and smooth muscle, as well as to areas of the central nervous system, thereby allowing for lower doses and less toxicity.

PepGen is currently advancing two rare genetic neuromuscular disease programs towards the clinic: one for DMD patients treatable with an exon 51 skipping oligonucleotide and the other targeting myotonic dystrophy type 1 (DM1). Proceeds from the financing will be used to advance lead programs EDO51 for DMD, entering phase 1 clinical trials in 2022, and EDODM1 for DM1, entering clinical trials in early 2023, as well as a pipeline of additional oligonucleotide candidates targeting neuromuscular, neurologic, and severe cardiac diseases. The funds will also enable expansion of PepGen’s team in Boston.

“We have shown in large animal studies that we can safely achieve industry-leading efficacy in exon 51 skipping, and we hope this will be transformative for DMD patients,” said James McArthur, president and CEO of PepGen. “We will build on this work to expand our DMD program and into other neuromuscular diseases, leveraging the enormous potential of our EDO platform technology to create a better future for people living with genetic diseases.”

PepGen’s lead DMD program, EDO51, targets the underlying cause of DMD, a rare genetic disease characterized by progressive muscle weakness, which leads to difficulties standing, walking, and breathing, ultimately impeding daily function and long-term survival. PepGen’s therapy combines an enhanced delivery peptide with a therapeutic oligonucleotide to target exon 51, stimulating exon-skipping to produce a functional dystrophin transcript enabling dystrophin production. Preclinical studies suggest that EDO51 can stimulate greater levels of exon-skipping that are expected to produce higher levels of dystrophin protein at lower doses than existing DMD therapies.

The company’s lead program in DM1, EDODM1, blocks the toxic CUG repeats that form hairpin loops in DMPK messenger RNA leading to myotonic dystrophy type 1, a progressive muscle disease that causes myotonia and worsening muscle loss. Similar to DMD, the long-term impacts of DM1 are overwhelming for families that live with this disease. PepGen’s approach delivers a peptide-conjugated antisense oligonucleotide to restore cellular function to multiple muscle tissue types. Clinical trials are expected to begin in early 2023.

PepGen will also expand its DMD program to include multiple patients amenable to exon skipping approaches beyond exon 51, including populations that have no approved or clinical-stage therapies available, and expects to develop a broad pipeline of therapeutic candidates to address neuromuscular and neurologic diseases in the coming years.

Photo: James McArthur, president and CEO of PepGen

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