PepGen Inc. (NASDAQ:PEPG), a clinical-stage biotechnology company advancing the next generation of oligonucleotide therapies with the goal of transforming the treatment of severe neuromuscular and neurological diseases, today announced promising clinical data from the 5 mg/kg multiple ascending dose cohort (MAD) of the ongoing Phase 2 FREEDOM2-DM1 trial in patients with myotonic dystrophy type 1 (DM1). The Company believes the totality of safety and efficacy results support the potential of the ongoing 10 mg/kg dose cohort, with clinical results expected in the second half of 2026.

"We are excited to share data from the lowest dose cohort in our multiple ascending dose study of PGN-EDODM1 in patients with DM1," said Paul Streck, MD, EVP Research and Development. "Overall, we are encouraged by the favorable safety and tolerability profile, and the positive trends exhibited with splicing improvement and vHOT. We look forward to reporting data from the ongoing 10 mg/kg multiple ascending dose cohort of FREEDOM2, which is more than halfway enrolled and remains on track to read out in the second half of this year."

FREEDOM2 Results for the 5 mg/kg (n=8) Dose Cohort

FREEDOM2 is a Phase 2 MAD, randomized, placebo-controlled clinical trial evaluating PGN-EDODM1 in patients with DM1, with planned dose escalation up to 12.5 mg/kg. The 5 mg/kg cohort enrolled eight patients, who received PGN-EDODM1 or placebo (randomized 6:2) every four weeks over a 12-week period. Key endpoints include safety, splicing correction and functional outcome measures. The data cutoff was March 4, 2026.

Splicing, Muscle Tissue Concentration and Functional Data:

  • Patients (n=6) treated with PGN-EDODM1 at 5 mg/kg demonstrated a mean splicing correction of 7.3%, compared to 6.8% in placebo-treated patients (n=2).
    • Excluding an outlier, patients showed a mean splicing correction of 22.9%. The outlier patient exhibited a worsening in splicing correction (70.8%), reducing the overall group mean to 7.3%.
  • Middle finger vHOT in the treatment group showed a positive trend of improvement versus a worsening observed in the placebo group. Both returned to baseline at Week 16.
  • Mean muscle tissue concentrations of PGN-EDODM1 available in 5 of 6 treated patients were 158 ng/g, as measured approximately one week after the fourth dose in the MAD study; one concentration readout remains pending.
  • No meaningful improvements were observed in 10-meter walk/run test (10MWRT) or handgrip strength at the starting PGN-EDODM1 dose of 5 mg/kg.

Safety and Tolerability Data:

  • PGN-EDODM1 was generally well-tolerated, with no serious adverse events (SAEs), all related treatment emergent adverse events (TEAEs) reported as mild and non-related TEAEs reported as mild or moderate
  • Nausea was the most common TEAE
  • No treatment-related discontinuations
  • No TEAEs related to renal function and no signs of cumulative toxicity

The Company is actively dosing the 10 mg/kg MAD cohort of FREEDOM2, with 5 of 8 patients receiving up to three doses of PGN-EDODM1, and expects to report data in the second half of 2026. In addition, 12 patients have currently enrolled in the open label extension (OLE) at 5 mg/kg, including 5 patients from FREEDOM2.