PepGen Inc. (NASDAQ:PEPG) shares are down during Tuesday’s premarket session following the announcement of topline results from the lowest dose cohort in the ongoing Phase 2 FREEDOM2-DM1 trial of PGN-EDODM1 for myotonic dystrophy type 1 (DM1).

Phase 2 Low-Dose Data Disappoints

The company on Monday reported in the 5 mg/kg cohort, a mean splicing correction of 7.3% was observed with PGN-EDODM1 compared to 6.8% with placebo.

The splicing deregulation induces an aberrant protein expression that provokes the loss of cell function and viability.

The stock fell as the data came lower than previously reported mean splicing correction at 5 mg/kg (n=6) and at 10 mg/kg (n=4) of 12.3% and 29.1%, respectively, demonstrating greater than dose-proportional increases in splicing correction.

Outlier Impact Weighs On Data

Excluding one outlier patient, the treatment group demonstrated 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%.

Functional Measures Show Mixed Signals

Middle finger vHOT in the treatment group showed a positive trend of improvement versus a worsening in the placebo group. Both returned to baseline at Week 16.

Video Hand Opening Time (vHOT) is a relatively simple and low-tech way to assess hand myotonia (delayed muscle relaxation).

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 the 10-meter walk/run test (10MWRT) or handgrip strength at the starting PGN-EDODM1 dose of 5 mg/kg.

Additionally, PepGen is actively dosing the 10 mg/kg cohort and expects to report clinical data in the second half of 2026.

The company has sufficient cash to fund operations into the second half of 2027.

PepGen Regulatory Overhang And Prior High-Dose Data

The U.S. Food and Drug Administration (FDA) in March placed the Phase 2 FREEDOM2-DM1 trial on a partial clinical hold due to questions regarding preclinical pharmacology and toxicology studies.

In September 2025, PepGen released data from the 15 mg/kg dose cohort of its ongoing FREEDOM-DM1 Phase 1 single ascending dose (SAD) study.

Mean splicing correction of 53.7% in patients receiving 15 mg/kg of PGN-EDODM1 (n=6), as measured by the 22-gene panel at 28 days post-dosing.

PEPG Stock Price Activity: PepGen shares were down 44.57% at $2.34 during premarket trading on Tuesday, according to Benzinga Pro data.

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