A Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping to Evaluate the Safety and Efficacy of ENTR-601-45

A 2-Part, Randomized, Double-Blind, Placebo-Controlled Study in Participants With Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping With an Initial Multiple Ascending Dose Part A to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ENTR-601-45, Followed by Part B to Evaluate the Safety and Efficacy of ENTR-601-45 (ELEVATE-45)

This is a study of the investigational medicine ENTR-601-45 in participants who have Duchenne muscular dystrophy (DMD), a rare genetic condition. The researchers want to: Test how safe ENTR-601-45 is, learn about any side effects, and look at the potential positive effects of ENTR-601-45, compared to placebo. Placebo looks like the investigational medicine but does not contain any active ingredient. In this summary ENTR-601-45 and placebo are both called study treatments.

The study has 2 parts: Part A: to evaluate if ENTR-601-45 is safe and to determine the best dose of ENTR-601-45 for Part B. Part B: to further evaluate the effect and safety of ENTR-601-45 at the dose determined in Part A. Participants will be able to roll into an open-label treatment period during which the safety and efficacy of extended dosing will be evaluated.

Participants will:

• Receive study treatment in the form of multiple intravenous (IV) infusions (slow injection) into a vein over the course of several weeks in Part A and in Part B
• Visit the clinic regularly for checkups and tests such as: blood and urine tests, physical examinations, questionnaires, muscle biopsies and exercise tests. Participants will have a muscle biopsy at the beginning of their participation and after their last dose to allow researchers to compare whether there have been changes in the muscle as a result of the study drug.

Participants are allowed to continue receiving their standard of care therapy for DMD during the study, as long as their health remains stable.

Inclusion Criteria:

1. Genetic diagnosis of DMD and confirmed pathologic variant in the dystrophin gene amenable to exon 45 skipping as reviewed by a central genetic counselor.
2. Assigned male at birth with clinical signs compatible with Duchenne muscular dystrophy as determined by the investigator.
3. Part A: 4-20 years of age, inclusive.
4. Ambulatory Status Part A: ambulatory with a Performance of the Upper Limb v2.0 (PUL 2.0) Entry as per protocol at Screening.
5. Adequate muscle for obtaining tissue biopsy as assessed by the investigator.
6. Other protocol-defined criteria apply.

Exclusion Criteria:

1. Any significant concomitant medical condition that might interfere with the ability to comply with protocol requirements.

2. Has an acute illness within 4 weeks prior to the first dose of study drug which may interfere with study measurements or jeopardize participant's safety.

3. Use of the following medications :

   1. Prior or current treatment with any exon skipping therapy within the previous 12 months
   2. Prior or current treatment with any gene therapy
   3. Use of anti-coagulants, anti-thrombotics, or anti-platelet agents from 30 days prior to screening and until the end of the study
   4. Use of an immunosuppressant (other than systemic or oral corticosteroid for DMD condition) from 30 days prior to screening until the end of the study.
   5. Treatment with a histone deacetylase (HDAC) inhibitor, including (but not limited to) givinostat from 30 days prior to screening until the end of the study

4. Laboratory abnormalities.

5. Daytime ventilator dependence or any use of invasive mechanical ventilation via tracheostomy.

6. Has an abnormal electrocardiogram (ECG) reading assessed as clinically significant by the investigator, and/or a QT interval with Fridericia correction method (QTcF) >450 msec at Screening or prior to the first dose of study drug on Day 1.

7. Received any experimental or investigational drug, etc. within 3 months prior to first dose or within 5 half-lives (whichever is longer).

8. Other protocol-defined criteria apply.