PepGen said an independent DSMB has cleared progression of its Phase II FREEDOM2-DM1 trial to the highest planned dose of 12.5 mg/kg and approved raising the OLE dose from 5 mg/kg to 10 mg/kg. The recommendations follow a safety review of the fully enrolled 10 mg/kg cohort and OLE data, with no SAEs, DLTs, or cumulative toxicity observed. Six of eight participants from the 5 mg/kg cohort have joined the OLE (total enrolment 16); 10 mg/kg results are due in November and 12.5 mg/kg data are expected in H1 2027.
DSMB Clears Dose Escalation to 12.5 mg/kg in PepGen’s FREEDOM2-DM1 Trial; OLE Raised to 10 mg/kg
Repeated doses at 5mg/kg and 10mg/kg have shown no signs of cumulative toxicity in the trial. Credit: rathshiki / Shutterstock.com.
PepGen announced that an independent Data and Safety Monitoring Board (DSMB) has approved advancing its Phase II FREEDOM2-DM1 trial of PGN-EDODM1 to the study's highest planned dose cohort of 12.5 mg/kg. The DSMB also recommended increasing the dose in the trial's open-label extension (OLE) from 5 mg/kg to 10 mg/kg. No amendments to the existing protocol are required for these changes.
The recommendations followed a safety review of the fully enrolled 10 mg/kg cohort alongside data from the OLE. PGN-EDODM1 has been generally well tolerated across both the FREEDOM2 study and the OLE: there have been no serious adverse events (SAEs), no dose-limiting toxicities (DLTs), no signs of cumulative toxicity with repeat dosing at 5 mg/kg and 10 mg/kg, and no participant discontinuations reported to date.
Enrollment and dosing updates: six of eight participants from the initial 5 mg/kg FREEDOM2 cohort have opted to join the OLE, bringing total programme enrolment to 16 participants. In the 10 mg/kg FREEDOM2 cohort, seven of eight participants have now completed dosing.
PepGen expects to report results from the 10 mg/kg FREEDOM2 cohort in November, and plans to present data from the upcoming 12.5 mg/kg cohort in the first half of 2027. An additional update from the OLE study is anticipated by early January. The company also plans to discuss next steps with regulators at an end-of-Phase II meeting.
James McArthur, President and CEO of PepGen, said: "The DSMB's recommendation to advance FREEDOM2 into the highest planned dose level and to escalate dosing in the OLE supports the encouraging safety profile of PGN-EDODM1 following multiple months of treatment. We look forward to reporting additional safety, splicing and functional data as we continue to evaluate the potential of PGN-EDODM1 to address the root cause of disease across multiple organ systems."
Regulatory context: PGN-EDODM1 has received Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration for the treatment of myotonic dystrophy type 1 (DM1). The European Medicines Agency has also granted orphan designation. In September 2025, PepGen's stock rose by more than 120% after the investigational DM1 candidate reported the highest mean splicing correction in a Phase I trial.
Source: Originally published by Clinical Trials Arena, a GlobalData brand. This summary consolidates PepGen’s announcement and related program details for clarity.
Help us improve.
