PepGen reports 46.5% splicing correction in DM1 trial
By Brie CarterKey points
- PepGen reported mean splicing correction of 46.5% in the 10 mg/kg cohort of its Phase 2 FREEDOM2-DM1 trial, representing the highest level reported to date in a multiple-dose study.
- The 12.5 mg/kg cohort is fully enrolled, with results expected in the first half of 2027. Additional safety and clinical data from FREEDOM-OLE are expected in January 2027.
- PepGen ended September 2026 with $104.8 million in cash, cash equivalents and marketable securities, which management expects to fund operations into 2028.
PepGen (NASDAQ:PEPG) reported positive clinical results from its Phase 2 FREEDOM2-DM1 trial, demonstrating mean splicing correction of 46.5% in the 10 mg/kg multiple ascending dose cohort evaluating PGN-EDODM1 for myotonic dystrophy type 1 (DM1).
The results represented the highest splicing correction reported to date in a multiple-dose study.
Five of six participants demonstrated greater than 20% splicing improvement, while four achieved improvements exceeding 50% at Week 13.
The company also reported improvements across several functional measures, including video Hand Opening Time (vHOT), hand grip strength, the 10-Meter Walk/Run Test and the Timed Up and Go assessment.
PGN-EDODM1 was generally well tolerated at the 10 mg/kg dose, with no treatment discontinuations, serious or severe adverse events, or dose-limiting toxicities reported in the cohort.
PepGen has completed enrollment in the 12.5 mg/kg FREEDOM2-DM1 cohort, with all participants having received up to three doses.
Results are expected in the first half of 2027.
The independent Data and Safety Monitoring Board also approved escalation in the FREEDOM-OLE extension study from 5 mg/kg to 10 mg/kg.
More than 35 doses at 10 mg/kg and 100 doses at 5 mg/kg have been administered, with 19 participants enrolled.
Interim 10 mg/kg safety and 5 mg/kg clinical data are expected in January 2027. One participant discontinued treatment following a hypersensitivity reaction.
PepGen also plans to initiate an expansion cohort alongside the third FREEDOM2 dose group to collect longer-term clinical data over a period of up to nine months.
Despite the positive findings, the FREEDOM2 programme remains subject to a partial FDA clinical hold issued in March 2026 following nonclinical findings in mice.
PepGen is conducting additional nonclinical studies and engaging with the FDA to address the agency's concerns.
Financially, PepGen reported a net loss of $19.4 million, or $0.28 per share, for the third quarter, compared with a loss of $18.0 million, or $0.52 per share, a year earlier.
Research and development expenses increased to $14.5 million from $13.4 million, while general and administrative expenses rose to $5.9 million from $5.2 million.
The company ended September 30, 2026, with $104.8 million in cash, cash equivalents and marketable securities.
Management expects its existing financial resources to support operations into 2028 based on currently planned activities.
