BrAAVe

This is a Phase 1/Phase 2 open-label single arm, multicenter, and multinational study with SAR446268 for treatment of male and female participants 10 to 50 years old with non-congenital myotonic dystrophy (DM) type 1 (DM1).

The purpose of this study is to evaluate the safety and efficacy of SAR446268 in knocking down dystrophia myotonica protein kinase (DMPK) messenger ribonucleic acid (mRNA) levels and improving neuromuscular function in DM1 participants receiving a single intravenous (IV) administration of SAR446268. The study consists of a dose escalation part (Part A) during which single ascending doses of SAR446268 will be evaluated in 3 distinct cohorts and an optional 4th dose cohort. Once a safe and effective dose is identified, additional participants will be treated in Part B, the dose expansion phase of the study.

The study duration will be 110 weeks (approximately 2 years) for each participant in Parts A and B respectively and includes a 6-week screening phase and a 104-week follow-up period post-SAR446268 administration.

Each participant meeting the eligibility criteria for each of the study parts will receive a single dose administration of SAR446268.

Inclusion Criteria: Participants are eligible to be included in the study only if all of

The following criteria apply:

• For Part A, participants must be 18 to 50 years of age inclusive, at the time of signing the informed consent.

• For Part B, participants must be as follows:

  • 10 to 17 years of age inclusive, at the time of signing the informed consent or,

  • 18 to 50 years of age inclusive, at the time of signing the informed consent.

• Participants with non-congenital onset DM1

• Participants presenting with signs of DM1 including myotonia and muscle weakness, as diagnosed previously by a clinician based on medical history.

• Participants with genetic diagnosis of DM1 [cytosine-thymine-guanine (CTG) repeat length ≥50 in one allele from medical history]

• Participants who can walk independently for at least 10 meters at screening (orthoses and ankle braces allowed).

• Participants who have been classified according to cardiac risk by the Investigator

As:

• Moderate risk participants with pacemaker and/or implantable cardioverter-defibrillator (ICD) for Part A

• Low, moderate, or high cardiac risk for Part B

Exclusion Criteria: Participants are excluded from the study if any of the following

Criteria apply:

• Participants with neutralizing antibodies against the AAV.SAN011 capsid

• Participants with left ventricular ejection fraction (LVEF) 2 x ULN and aspartate aminotransferase (AST) >2 x ULN

  • Alkaline phosphatase >2 x ULN

  • Total bilirubin >1.5 x ULN (unless has a genetically confirmed diagnosis of Gilbert's syndrome)

  • Direct bilirubin ≥1.5 x ULN

  • Participants with International normalized ratio >1.5

• Participants with renal disease defined as: • Serum creatinine >1.5 x ULN and/or estimated glomerular filtration rate