Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy

This is a Phase 2, multicenter, open-label study of KER-065.

The study will consist of 3 periods:

* Screening Period (up to 6 weeks)
* Treatment Period (48 weeks)
* Safety Follow-up Period (4 weeks)

Participants will be enrolled in parallel into 1 of 3 treatment cohorts:

* Cohort A1 (Late Ambulatory)
* Cohort A2 (Late Ambulatory)
* Cohort N1 (Early Nonambulatory)

• KER-065 (Drug), also known as Rinvatercept: KER-065 will be administered subcutaneously (SC)

Primary outcomes

• Number of participants with treatment-emergent adverse events (TEAEs and serious adverse events (SAEs) [Up to approximately 14 months]: To evaluate the safety and tolerability of KER-065 in ambulatory and nonambulatory participants with DMD

Secondary outcomes

• KER-065 serum concentration by visit, as appropriate [Up to Week 52]: To assess the pharmacokinetics (PK) of KER-065 in ambulatory and nonambulatory participants with DMD
• Number and proportion of participants with treatment-emergent ADA (antidrug antibody) by visit [Up to Week 52]: To assess the immunogenicity of KER-065 in ambulatory and nonambulatory participants with DMD
• Change from baseline by visit in bone mineral density (BMD), fat mass, and lean body mass, as measured by dual- energy X-ray absorptiometry (DXA) [Week 12, Week 24 and Week 48]: To assess the effect of KER-065 on body composition in ambulatory and nonambulatory participants with DMD
• Change from baseline by visit in muscle volume and intramuscular fat by skeletal muscle Magnetic Resonance Imaging (MRI) [Week 24 and Week 48]: To assess the effect of KER-065 on skeletal muscle in ambulatory and nonambulatory participants with DMD
• Ambulatory: Change from baseline by visit in North Star Ambulatory Assessment (NSAA) total score [Week 24 and Week 48]: To assess the effect of KER-065 on motor function in ambulatory participants with DMD
• Ambulatory: Change from baseline by visit in 4-stair climb (4SC) [Week 24 and Week 48]: To assess the effect of KER-065 on motor function in ambulatory participants with DMD
• Ambulatory: Change from baseline by visit in 10-meter walk/run (10MWR) test [Week 24 and Week 48]: To assess the effect of KER-065 on motor function in ambulatory participants with DMD
• Ambulatory: Change from baseline by visit in time to rise (TTR) [Week 24 and Week 48]: To assess the effect of KER-065 on motor function in ambulatory participants with DMD
• Nonambulatory: Change from baseline by visit in Performance of Upper Limb (PUL) v2.0 score [Week 24 and Week 48]: To assess the effect of KER-065 on motor function in nonambulatory participants with DMD

Sex: Male, ages: 9 Years to any

Key Inclusion Criteria:

* Diagnosis of DMD, defined as the presence of phenotypic features at screening consistent with DMD AND documented mutation in the dystrophin gene consistent with the diagnosis of DMD using a clinically validated genetic test.
* Receiving a stable regimen of systemic CS (including, but not limited to, prednisone, prednisolone, deflazacort, or vamorolone) for at least 90 days before screening.
* Body weight of ≥ 25.0 kg.

Ambulatory Participants Only (Cohort A1 and A2):

* Ambulatory, defined as able to walk independently without assistive devices.
* Able to TTR in < 10 seconds.
* Has a NSAA score ≥ 15 points.
* Cohort 2 only: Documentation of a stable dose of an approved exon-skipping therapy.

Nonambulatory Participants Only (Cohort N1):

* Nonambulatory, characterized as being unable to ambulate for a minimum of 3 months before first dose with onset of nonambulatory status AND a NSAA walk score of 0 and inability to perform the 10MWR.
* PUL v2.0 entry item score of 3 to 5, inclusive.

Key Exclusion Criteria:

* Clinical symptoms or signs of cardiomyopathy or heart failure.
* Exposure to any approved or investigational dystrophin restoration gene therapy product.
* Exposure to any approved or investigational dystrophin restoration product other than gene therapy (Except for exon-skipping therapy for Cohort A2).
* Exposure to any approved or investigational histone deacetylase inhibitor, antimyostatin therapy, therapy targeting transforming growth factor-beta ligands, or cell-based therapy.
* Use of any other pharmacological treatment, except for CS
* Treatment with immunosuppressant therapy (other than CS)
* History of fracture of the upper limb

Nonambulatory Participants Only (Cohort N1):

* Elbow-flexion contractures > 30° in both upper extremities.
* Forced vital capacity (FVC) of < 50% or requirement for daytime or nocturnal ventilation, except for nocturnal non-invasive ventilation AND inability to perform consistent FVC measurements within ± 15% during paired testing.