Delpacibart Etedesiran

PepGen Inc. (Nasdaq: PEPG) announced that the US FDA has placed a partial clinical hold on the FREEDOM2-DM1 Phase II study 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 US 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 I FREEDOM study, which PepGen had submitted to support initiation of FREEDOM2 in the United States. No US 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. FREEDOM2 is designed as a multiple ascending dose, randomized, placebo-controlled study. Regulatory holds related to safety or preclinical data are not uncommon in the oligonucleotide field. For example, the FDA placed a partial hold on Avidity Biosciences’ AOC-1001 program in 2022 and paused Amylyx’s AMX0114 antisense therapy during early clinical review, both of which were later resolved after additional safety analyses. 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. Outside the United States, PepGen received regulatory clearance to initiate FREEDOM2 in South Korea, Australia, and New Zealand. Dosing of the 10 mg/kg cohort continues in the United Kingdom and Canada, following a Data Safety Monitoring Board recommendation to dose escalate. Patients from the FREEDOM and FREEDOM2 studies in Canada are continuing into an Open Label Extension study, and PepGen has received regulatory clearance for the OLE in the UK. PGN-EDODM1 is among several clinical-stage candidates in development for DM1, including Dyne Therapeutics’ DYNE-101 and Avidity Biosciences’ AOC 1044, both of which use alternative delivery approaches to target DMPK mRNA. None of these programs has yet reached a regulatory filing stage. PepGen reiterated its guidance for reporting data from the FREEDOM2 5 mg/kg cohort in the first quarter of 2026 and from the 10 mg/kg cohort in the second half of 2026. The company stated it is committed to addressing the FDA’s preclinical questions and maintaining trial progress at sites outside the United States. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website