PepGen's enhanced delivery oligonucleotide (EDO) cell-penetrating peptide technology is engineered to optimize tissue delivery and cellular uptake of therapeutic oligonucleotides PGN-EDODM1 is being evaluated for the treatment of myotonic dystrophy type 1 (DM1). PGN-EDODM1 binds to toxic CUG repeat expansion (CUGexp) in DMPK mRNA and acts to liberate sequestered MBNL1 protein without degrading DMPK transcript. Release of MBNL1 protein is hypothesized to restore the splicing profiles of multiple downstream transcripts; a central cause of DM1 pathology. Men and women, 18-50 years of age, inclusive, with genetically confirmed diagnosis of DM1 will be randomized 3:1 (6 active, 2 placebo) to receive PGN EDODM1 or placebo in each dose cohort. The primary objective of this single-ascending dose (SAD) study is to evaluate the safety and tolerability of PGN-EDODM1 in adults living with DM1. Secondary and exploratory objectives include pharmacokinetics (PK), concentration of PGN-EDODM1 in skeletal muscle, and pharmacodynamics (changes in splicing pattern of affected transcripts). A muscle needle biopsy (tibialis anterior) will be performed at baseline and at Weeks 4 and 16 post-dosing for measurement of tissue drug concentrations and splicing of selected transcripts. Exploratory measures such as video hand opening time to assess myotonia and functional measures will be included to inform future studies. This Phase 1 SAD clinical study will support continued development of PGN-EDODM1 for the treatment of the root cause of DM1. PepGen's enhanced delivery oligonucleotide (EDO) cell-penetrating peptide technology is engineered to optimize tissue delivery and cellular uptake of therapeutic oligonucleotides PGN-EDODM1 is being evaluated for the treatment of myotonic dystrophy type 1 (DM1). PGN-EDODM1 binds to toxic CUG repeat expansion (CUGexp) in DMPK mRNA and acts to liberate sequestered MBNL1 protein without degrading DMPK transcript. Release of MBNL1 protein is hypothesized to restore the splicing profiles of multiple downstream transcripts; a central cause of DM1 pathology. Men and women, 18-50 years of age, inclusive, with genetically confirmed diagnosis of DM1 will be randomized 3:1 (6 active, 2 placebo) to receive PGN EDODM1 or placebo in each dose cohort. The primary objective of this single-ascending dose (SAD) study is to evaluate the safety and tolerability of PGN-EDODM1 in adults living with DM1. Secondary and exploratory objectives include pharmacokinetics (PK), concentration of PGN-EDODM1 in skeletal muscle, and pharmacodynamics (changes in splicing pattern of affected transcripts). A muscle needle biopsy (tibialis anterior) will be performed at baseline and at Weeks 4 and 16 post-dosing for measurement of tissue drug concentrations and splicing of selected transcripts. Exploratory measures such as video hand opening time to assess myotonia and functional measures will be included to inform future studies. This Phase 1 SAD clinical study will support continued development of PGN-EDODM1 for the treatment of the root cause of DM1.