PepGen’s plans to get a second oligonucleotide therapy into the clinic have hit a regulatory roadblock courtesy of a clinical hold notice from the FDA.
Rather than launch the phase 1 trial in the first half of the year as previously planned, the Boston-based company will now wait to receive a formal letter from the regulator explaining why the study application has been turned down. The candidate, dubbed PGN-EDODM1, was due to be assessed in patients with myotonic dystrophy type 1, a genetic disorder that can cause muscle loss and weakness.
“We are disappointed to receive a clinical hold notice on our planned PGN-EDODM1 study in the U.S., and we will work closely with the FDA to lift the hold as quickly as possible,” CEO James McArthur, Ph.D., said in a postmarket release Tuesday. “In parallel, we continue to pursue the advancement of PGN-EDODM1 into the clinic outside the U.S.”
PGN-EDODM1 consists of PepGen’s cell-penetrating peptide conjugated to a steric-blocking oligonucleotide cargo. In December, the biotech touted preclinical data showing the therapy was well tolerated in rodent and nonhuman primates. It also didn’t degrade DMPK transcripts, a potentially important safety benefit, in studies of patient cells, the company noted at the time.
PepGen ended March with $164.5 million in cash and equivalents, which is estimated to last into 2025. McArthur said in yesterday’s release that the biotech remains “well capitalized” to fund the ongoing development of both PGN-EDODM1 and the company’s lead asset PGN-EDO51.
PGN-EDO51 has enjoyed better luck with regulators, with Health Canada giving the green light May 18 for a phase 2 study in Duchenne muscular dystrophy (DMD) amenable to an exon 51 skipping approach. The biotech stressed in the release that the FDA’s hold on PGN-EDODM1 doesn’t impact the clinical development of PGN-EDO51.
PGN-EDO51 is a therapeutic oligonucleotide that targets exon 51 to treat a subset of DMD patients. Like Sarepta Therapeutics' Exondys 51, the drug is designed to mask exon 51 and thereby enable patients to produce the functional dystrophin needed to strengthen muscle fibers.
As well as launching the phase 2 trial of PGN-EDO51 in Canada in the first half of the year, PepGen is planning a multinational midstage study of the therapy to begin in the second half of 2023. The company also has three other preclinical DMD candidates in early stages of development.
PepGen’s stock dropped nearly 10% to $14.25 in premarket trading Wednesday from a closing price of $15.78.