This is a phase 1/2a double-blinded, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses of ARO-DM1 compared to placebo in male and female subjects with type 1 myotonic dystrophy (DM1). Participants who have provided written informed consent and met all protocol eligibility requirements will be randomized to receive single (Part 1) or multiple (Part 2) doses of ARO-DM1 or placebo.

Inclusion Criteria:

• Genetically confirmed diagnosis of DM1
• Clinician-assessed signs of DM1 including clinically apparent myotonia
• Onset of DM1 symptoms occurred after the age of 12 years
• Walk for at least 10 meters independently at Screening
• Subjects of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of study or last dose of study drug, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days following the end of study or last dose of study drug whichever is later.

Exclusion Criteria:

• Inadequately controlled diabetes
• Confirmed diagnosis of congenital DM1
• Uncontrolled hypertension
• History of tibialis anterior (TA) biopsy within 3 months of Day 1 or planning to undergo TA biopsies during the study period
• Clinically significant cardiac, liver or renal disease
• HIV infection (seropositive) at Screening
• Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at screening
• Untreated or poorly controlled epilepsy
• Treatment with anti-myotonia medication within a period of 5 half-lives of the medication prior to Screening.
• Abnormal coagulation parameters at Screening including platelet count, international normalized ratio (INR), prothrombin time, and activated partial thromboplastin time (APTT)

Note: Additional inclusion/exclusion criteria may apply per protocol