PepGen Ltd reported results from the 5 mg/kg multiple ascending dose cohort of its Phase 2 FREEDOM2-DM1 trial and saw its shares fall 44% in after-hours trading on Monday. The company released data showing limited separation between active treatment and placebo on the trial's primary biomarker measurement.
In the 5 mg/kg cohort, mean splicing correction with PGN-EDODM1 measured 7.3% compared with 6.8% for placebo. The cohort comprised eight patients randomized 6:2 to receive either PGN-EDODM1 or placebo every four weeks over a 12-week period. Six patients received active treatment and two received placebo.
PepGen highlighted that one treated patient was an outlier who demonstrated a substantial worsening in splicing correction of 70.8%, which pulled down the overall mean for the treated group. Removing that single outlier, the remaining five patients who received PGN-EDODM1 showed a mean splicing correction of 22.9%.
At the 5 mg/kg dose level, the trial did not record meaningful improvements on functional measures. Specifically, no significant gains were observed on the 10-meter walk/run test or in handgrip strength.
The company reported that PGN-EDODM1 was generally well tolerated in this cohort. No serious adverse events were reported, and all treatment-emergent adverse events considered related to dosing were classified as mild. Nausea was the most frequently reported adverse event. There were no treatment-related discontinuations and no adverse events linked to renal function.
Muscle tissue concentrations of PGN-EDODM1 were measured in five of six treated patients approximately one week after the fourth dose, with a mean concentration of 158 ng/g reported for those measurements.
PepGen is actively dosing the 10 mg/kg multiple ascending dose cohort of FREEDOM2, with five of eight patients having received up to three doses so far. The company intends to report data from the higher-dose cohort in the second half of 2026. PepGen also stated it has sufficient cash to fund operations into the second half of 2027.
Context and next steps
The 5 mg/kg cohort results show limited biomarker separation from placebo and no meaningful functional benefit at this dose level. Investors will be watching the 10 mg/kg cohort results due in the second half of 2026 for additional evidence on dose response. The company has indicated a cash runway into the second half of 2027.