Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants with Myotonic Dystrophy Type 1

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• 1. Previous or ongoing medical condition, medical history, physical findings, or laboratory abnormalities that in the opinion of the Investigator could affect safety, make it unlikely that dosing schedule and follow-up will be correctly completed, and/or impair the assessment and interpretation of study results 2. History of major surgical procedure within 12 weeks prior to the start of investigative product administration or an expectation of a major surgical procedure (eg, implantation of cardiac defibrillator) during course of the study 3. History of anaphylaxis 4. History of clinically significant liver disease or ongoing treatment for liver disease, or confirmed elevated alanine aminotransferase (ALT) > 3× upper limit of normal (ULN), at Screening. 5. History of clinically significant hematologic disease or have any of the following hematologic results at Screening: platelets or hemoglobin below the lower limit of normal for age and sex. 6. History of clinically significant kidney disease, ongoing treatment for kidney disease (treatment for hypertension is permitted) or estimated glomerular filtration rate (eGFR) < 60 mL/min as calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Cystatin C Equation at screening 7. Active malignancy or history within the last 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated 8. Recent history (within previous 12 months) of drug or alcohol abuse 9. Medical condition other than DM1 that would significantly impact ambulation or participation in functional assessments 10. Current insulin-dependent diabetes mellitus or uncontrolled diabetes mellitus, congestive heart failure, symptomatic cardiomyopathy, symptomatic coronary artery disease, multiple sclerosis, or other serious medical illness
• 11. Second- or third-degree heart block, symptomatic first-degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmias, pacemakers, implanted defibrillator, or is receiving medication for treatment of cardiac arrhythmia 12. Treatment with medications that can improve myotonia or clinical functional endpoints within a period of 5 half-lives of the medication prior to performing screening assessments. May include but not limited to mexiletine, phenytoin, carbamazepine, procainamide, disopyramide, ranolazine, flecainide, lamotrigine, nifedipine, acetazolamide, clomipramine, imipramine, amitriptyline, taurine, quinine, or metformin. 13. Use of anticoagulant such as warfarin or a direct oral anticoagulant (eg, dabigatran) due to the increased risk of bleeding 14. Current treatment with immunosuppressive therapy 15. Receipt of another investigational drug, biologic agent, or device within 5 half-lives (if known) of the agent, or within 4 months prior to the start of Screening, whichever is longer. Individuals previously treated with oligonucleotide therapies (including small interfering RNA [siRNA]) may be eligible if the last dose of the investigational drug was received ≥ 3 years ago 16. ECG with the corrected QT interval by Fridericia's Formula (QTcF) ≥450 ms in men and QTcF ≥ 460 ms in women, PR ≥ 240 ms, left bundlebranch block, or a conduction defect, which is clinically significant in the opinion of the Investigator 17. Percent predicted forced vital capacity (FVC) < 50% 18. History of tibialis anterior biopsy within 3 months of Day 1 or planning to undergo tibialis anterior biopsies during study period for reasons unrelated to the study 19. Inability, or impaired ability, to complete study procedures and/or complete the study, due to physical or cognitive impairment, in the judgment of the Investigator 20. Inability to undergo venipuncture successfully or tolerate venous access 23. Use of glucagon-like peptide 1 (GLP-1) agonist medications including semaglutide, dulaglutide, liraglutide, exenatide, or tirzepatide within a period of 5 half-lives of the medication prior to performing screening assessments. 24. Use of nephrotoxic medications within a period of 5 half-lives of the medication prior to performing screening assessments. May include, but are not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides (eg, gentamicin, streptomycin), bisphosphonates, and antiviral agents (eg, acyclovir, adefovir). Planned procedures that require contrast during the study are also exclusionary. 25. Acute kidney injury within 12 weeks prior to Screening, characterized by an increase in serum creatinine of 0.3 mg/dL within 48 hours, or of 1.5-fold within a week (Khwaja 2012) 26. Hematuria > 5 red blood cells per high power field (RBC/HPF) on urinalysis at Screening 27. Persistent systolic blood pressure < 90 mm Hg or signs or symptoms of hypotension or volume depletion/dehydration 28. Prior history of deep vein thrombosis (DVT) or pulmonary embolism (PE) 29. Recent physical inactivity (eg, immobilization of ≥ 3 days)