PepGen Reports 46.5% Splicing Correction in DM1 Trial

Daniel Okafor

PepGen reported 46.5% mean splicing correction in the 10 mg/kg cohort of its Phase 2 FREEDOM2-DM1 trial for myotonic dystrophy type 1. The company ended the third quarter of 2026 with $104.8 million in cash and investments and expects that balance to support planned operations into 2028.

The positive cohort strengthens PepGen's case for a higher-dose test. An independent monitoring board recommended moving to 12.5 mg/kg, FREEDOM2-DM1's third and highest dose, with results expected in the first half of 2027. The U.S. portion remains under a partial FDA hold, however.

What did the 10 mg/kg cohort show?

PepGen said the 46.5% result represented the highest mean splicing correction reported in a multiple-dose study. Five of six treated participants showed more than 20% improvement. Four exceeded 50% at week 13.

The company also reported improvements in hand opening, grip strength, walking and mobility. Those functional gains broaden the result beyond the splicing measure. PepGen did not quantify them in the announcement, leaving the precision of the clinical benefit less clear than the 46.5% headline.

James McArthur, PhD, President and Chief Executive Officer of PepGen, said: “The positive 10 mg/kg cohort results we announced today were made possible by our team’s focused execution. We are very confident in PGN-EDODM1’s potential to deliver meaningful benefit to the DM1 community.”

Did safety support a higher dose?

PepGen described PGN-EDODM1 as generally well tolerated at 10 mg/kg. The company reported no treatment discontinuations, serious or severe adverse events, or dose-limiting toxicities in the cohort.

An independent monitoring board recommended advancing FREEDOM2-DM1 to its third and highest-dose cohort at 12.5 mg/kg. PepGen said that cohort is fully enrolled and participants have received as many as three doses. PepGen expects results during the first half of 2027.

The dose step converts a positive cohort into a direct test at the trial's planned ceiling. It also removes recruitment from the immediate critical path, because PepGen has already enrolled the higher-dose group.

What will the extension study add?

PepGen is also continuing an open-label extension study. The company expects interim safety data from the 10 mg/kg group and clinical data from participants receiving 5 mg/kg in January 2027.

The January package will extend the safety record and add lower-dose clinical evidence. It will also arrive before the higher-dose results. That sequence gives investors two dated 2027 readouts before the higher-dose cohort reports.

What does the FDA hold mean?

The FDA placed the U.S. portion of FREEDOM2 under a partial clinical hold in March after findings from mouse studies. PepGen is conducting additional nonclinical work and remains in discussions with the agency.

Trials outside the United States continue. The hold therefore constrains the U.S. portion while the international program remains active. The immediate gating issue for U.S. testing is further nonclinical work and an FDA decision, not enrollment in the 12.5 mg/kg cohort.

How did spending and losses change?

PepGen reported these expense and loss figures:

• Research and development: Expense increased to $14.5 million from $13.4 million.
• General and administrative: Expense rose to $5.9 million from $5.2 million.
• Net loss: The quarterly loss widened to $19.4 million, or $0.28 per share, from $18 million, or $0.52 per share.

Research spending increased $1.1 million. Administrative spending rose $0.7 million. The dollar loss grew $1.4 million, while loss per share fell $0.24. The two figures point in opposite directions, and PepGen's results do not explain the divergence.

Cash and investments provide the stated funding buffer. PepGen ended the quarter with $104.8 million in cash and investments and expects the balance to support planned operations into 2028. That timeline extends beyond both 2027 readout windows, although it does not set a date for U.S. regulatory clearance.

What are the next proof points?

PepGen now has three concrete proof points: extension data in January 2027, results from the fully enrolled 12.5 mg/kg cohort in the first half of 2027, and progress in FDA discussions. The first two will extend the efficacy and safety evidence. The third governs when the U.S. portion can move again.

The sequence matters more than the 46.5% headline alone. PepGen needs higher-dose efficacy, extension safety and regulatory resolution before its stated cash runway reaches 2028. McArthur's confidence in PGN-EDODM1 is clear; the clinical and regulatory proof remains dated, specific and unfinished.