PepGen Inc. (Nasdaq: PEPG) announced that the U.S. Food and Drug Administration has placed a partial clinical hold on the FREEDOM2-DM1 Phase 2 multiple ascending dose, randomized, placebo-controlled clinical trial of PGN-EDODM1, a peptide-conjugated antisense oligonucleotide under development for the treatment of myotonic dystrophy type 1 (DM1). The partial clinical hold applies to U.S. trial activity only, while dosing continues at international sites.
The FDA's partial clinical hold relates to questions about previously submitted preclinical pharmacology and toxicology studies. The agency did not cite concerns regarding blinded clinical data from the earlier Phase 1 FREEDOM study, which PepGen had submitted to support initiation of FREEDOM2 in the United States. No U.S. patients had been enrolled in the FREEDOM2 trial at the time of the hold. PepGen stated it is submitting additional analyses to the FDA, including recently unblinded FREEDOM data, and intends to work with the agency to resolve the questions. A partial clinical hold permits ongoing treatment of already-enrolled patients but restricts new enrollment at affected sites.
PGN-EDODM1 uses PepGen's proprietary Enhanced Delivery Oligonucleotide (EDO) platform, which conjugates cell-penetrating peptides to antisense oligonucleotides to improve cellular uptake in muscle tissue. The molecule binds to pathogenic CUG trinucleotide repeat expansions in DMPK mRNA, disrupting sequestration of the MBNL1 splicing protein and restoring normal RNA splicing function. DM1 is a severe neuromuscular disease with no FDA-approved disease-modifying therapies. Current management is limited to symptomatic treatment. The FDA has granted PGN-EDODM1 both Orphan Drug Designation and Fast Track Designation for DM1, and the European Medicines Agency has granted Orphan Designation.
PepGen was founded in 2018 as a spinout from the University of Oxford, where the EDO platform technology was developed. The company holds a license agreement with Oxford for the foundational intellectual property. PepGen completed its initial public offering on Nasdaq in May 2022 and has retained full development and commercial rights to PGN-EDODM1 without entering into any disclosed partnership or sublicensing arrangement.