Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply at
screening:
1. Age ≥ 16 years at the time of signing the informed consent/assent form.
2. Diagnosis of DM1 confirmed by molecular genetics with trinucleotide repeat size > 100.
Historical results from clinical testing are acceptable.
3. Clinically apparent myotonia equivalent to hand opening time of at least 2 seconds as
determined by a central reading of vHOT (middle finger) values.
4. Hand grip strength averaged from both sides ≥ 5% and ≤ 85% predicted of normal.
5. 5×STS completion in ≥ 8 seconds without the use of assistive devices such as canes,
walkers, or orthoses. The use of submalleolar orthoses and inserts or supports that do not
extend above the malleolus are permitted during testing.
6. Able to complete 10-MWRT without the use of assistive devices such as canes, walkers,
or orthoses. The use of submalleolar orthoses and inserts or supports that do not extend
above the malleolus are permitted during testing.
7. Body mass index (BMI) 8. If being treated with testosterone, on a stable replacement dose for 30 days prior to
screening.
9. Participants must agree to follow protocol-specified highly effective contraception
guidance as described in the protocol.
10. Female participants must not be pregnant or breastfeeding.
11. Capable of giving signed informed consent/assent as described in the protocol, which
includes compliance with the requirements and restrictions listed in the informed consent
form (ICF) and in the protocol and authorization to use health information that is
confidential according to national and local privacy regulations.
12. Willingness and ability of participant to comply with and tolerate scheduled visits, dosing
administration plan, and study assessments over the duration of the study.
13. For France Only: According to the Article L1124-1 of the French Public Health Code,
only individuals with social security or similar coverage are eligible for this study.

Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply at screening:
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 the 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 (based on Investigator judgment) within 12 weeks
prior to the start of screening, with the exception of implanted pacemaker or defibrillator,
or an expectation of a major surgical procedure during the Placebo-Controlled Period of
the study (based on Investigator judgment).
3. History of DVT or PE within the last 5 years.
4. A known diagnosis of congenital DM1.
5. History of clinically significant liver disease or ongoing treatment for liver disease or
confirmed elevated ALT > 3 × ULN at screening.
6. 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.
7. History of clinically significant kidney disease, ongoing treatment for kidney disease
(treatment for hypertension is permitted) or eGFR Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Cystatin C Equation.
8. 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.
9. Hematuria > 5 red blood cells per high power field (RBC/HPF) on urinalysis at
screening.
10. Persistent systolic blood pressure volume depletion/dehydration.
11. 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
excised and considered cured at least 1 year prior to Screening. Participants with cancers
in remission for >5 years prior to Screening may be included after discussion with the
Medical Monitor.
12. Medical condition other than DM1 that would significantly impact ambulation or
participation in functional assessments.
13. Uncontrolled diabetes mellitus or other serious medical illness that may complicate
interpretation of safety or efficacy in the study, in the opinion of the Investigator.
14. Individuals with a presence of second- or third-degree heart block, ventricular
arrhythmias, 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 bundle-branch block,
or a conduction defect that is clinically significant in the opinion of the Investigator are
excluded unless they have a pacemaker or defibrillator that was implanted more than
2 weeks prior to screening.
DYNE101-DM1-301 Dyne Therapeutics, Inc
Original Protocol 17 October 2025
Confidential Page 49 of 106
15. Individuals with known structural heart disease, evidence of noncompaction
cardiomyopathy, or a known (at most recent imaging) left ventricular ejection fraction of
16. Individual has a history of suicide attempt, suicidal behavior, or has any suicidal ideation
within 6 months prior to Screening that meets criteria at a level of 4 or 5 of the C-SSRS
or who, in the opinion of the Investigator, is at significant risk to commit suicide.
17. 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, or quinine.
18. Current treatment with systemic immunosuppressive therapy.
19. Use of glucagon-like peptide 1 (GLP-1) agonist/incretin medications including
semaglutide, dulaglutide, liraglutide, exenatide, or tirzepatide within a period of
5 half-lives of the medication prior to performing screening assessments.
20. Use of nephrotoxic medications within a period of 5 half-lives of the medication prior to
performing screening assessments. These may include, but are not limited to,
nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides (eg, gentamicin and
streptomycin), bisphosphonates, and antiviral agents (eg, acyclovir and adefovir).
Planned procedures that require contrast during the study are also exclusionary.
21. Receipt of any prior gene therapy, or 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.
NOTE: Individuals who have participated in non-interventional, natural history studies
are eligible to participate in this study. Ongoing participation in a natural history study is
not permitted from the day of first study drug administration until the participant has
completed this study unless prior permission granted by the study medical monitor.
22. Percent predicted FVC 23. Recent physical inactivity (eg, immobilization of ≥ 3 days) if, in the opinion of the
Investigator, this would hinder the participant from complying with study requirements.
24. Inability to undergo venipuncture successfully or tolerate venous access.
25. Inability, or impaired ability, to complete study procedures and/or complete the study,
due to physical or cognitive impairment or illicit drug or alcohol abuse, in the judgment
of the Investigator.
26. For France Only: According to the Articles L1121-8 and L1122-2 of the French Public
Health Code, individuals under legal guardianship, curatorship, or judicial protection are
not eligible for this study.