PepGen’s stock has skyrocketed after a Phase II trial of its enhanced delivery oligonucleotide (EDO) for a rare muscle dystrophy met its endpoints, with the company touting the highest level of genetic modulation ever seen in this type of study.
The FREEDOM2-DM1 trial (NCT06667453) evaluated PGN-EDODM1 in patients with myotonic dystrophy type 1 (DM1), a rare, progressive, and multisystemic genetic disease.
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Upon unveiling the data, Nasdaq-listed PepGen’s stock rose 132.22% between its 9 November market close ($2.39) to 10 November open ($5.55). The company’s stock did drop slightly during the day, closing at $4.61; however, this is still an impressive 92.9% rise on the 9 November close.
The trial data showed the highest level of splicing correction ever reported in a multiple-dose study for DM1, as well as notable improvements across multiple functional measures including myotonia, strength, ambulation, and mobility following four monthly doses of PGN-EDODM1. Mean splicing correction in muscle reached 46.5%, with five of six patients having more than 20% splicing correction and four patients showing more than 50% splicing correction, as measured by the 22-gene panel after 13 weeks. Meanwhile, mean splicing correction in the pooled placebo group was 6.8% at the same time point.
There were also sustained improvements recorded in video Hand Opening Time (vHOT), hand grip strength, 10-Meter Walk/Run Test (10MWRT), and Timed Up and Go (TUG) assessments, providing compelling evidence of PGN-EDODM1’s potential to address multiple clinical manifestations of DM1 and supporting continued development.
Hand grip strength improved by approximately 16.2% after 16 weeks of treatment, corresponding to a 6.3-point improvement in maximum predicted per cent normal (PPN) from baseline, while placebo improved 0.9 PPN.
PGN-EDODM1 was generally well tolerated at 10mg/kg, supporting continued clinical development. All reported treatment-emergent adverse events (TEAEs) in the 10 mg/kg cohort were mild or moderate, and no treatment discontinuations were reported.
Dr Hanns Lochmüller, professor of neurology at the University of Ottawa and a FREEDOM2 study investigator, said: “DM1 is a multisystemic disease, placing a major burden on patients and their families. The improvements observed across myotonia, mobility and grip strength are encouraging because they reflect functions that affect patients’ daily lives. The relationship between splicing correction and improvements in myotonia is particularly interesting, and longer-term follow-up will be important to better understand the durability and clinical relevance of these findings.”
FREEDOM2-DM1 is an ongoing, randomised, double-blind, placebo-controlled trial which is investigating the EDO at varying doses. The 12.5mg/kg cohort of FREEDOM2 is fully enrolled, with data expected in the first half of 2027. PepGen also expects to report interim clinical data at 5mg/kg and safety data at 10mg/kg from the open-label extension study in January 2027.
DM1 is an inherited, multisystemic genetic disorder that causes progressive muscle weakness, myotonia (the inability to relax muscles after contraction), and complications in multiple organs, including the heart, lungs, eyes, and endocrine system. Currently, treatment involves a multidisciplinary, symptom-based management approach to improve safety and quality of life, which includes muscle and myotonia management, cardiac care and respiratory care.
Novartis previously had hopes for success in this patient population; however, a Phase III trial of its $12bn Avidity Biosciences-acquired therapy, delpacibart etedesiran, failed to show any statistical benefit.
