Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta

Key Inclusion Criteria:

• Clinical diagnosis of OI Type I, III, or IV confirmed by identification of geneticmutation in COL1A1 or COL1A2

• History of ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months,or ≥ 1 femur, tibia, or humerus fracture in the past 24 months

• Any prior exposure to, or currently receiving, IV-bisphosphonate therapy fortreatment of OI

• Serum 25-hydroxyvitamin D level ≥ 20 ng/mL at the Screening visit. If 25-hydroxyvitamin D levels are below 20 ng/mL, the subject may be rescreened after aminimum of 14 days of vitamin D supplementation as directed by the Investigator

Exclusion Criteria:

• History of skeletal malignancies or bone metastases at any time

• History of neural foraminal stenosis (except if due to scoliosis)

• Clinical manifestations of Chiari malformation or basilar invagination. Presence ofany other neurologic disease that has been clinically unstable within past 2 yearsrequires review by the Medical Monitor.

• History of or current uncontrolled concomitant diseases that may impact bonemetabolism, such as hypo/hyperparathyroidism, abnormal thyroid function, nephroticsyndrome, or Stage IV/V renal disease

• Any skeletal condition (other than OI) leading to bone deformity and/or increasedrisk of fractures, such as rickets, osteopetrosis, idiopathic juvenile osteoporosis,or skeletal dysplasia

• History of known cardiovascular disease such as coronary artery anomaly, Kawasakidisease, myocarditis, cardiomyopathy, myocardial infarction, stroke, orthromboembolic disease. Individuals with other congenital or acquired cardiovasculardisease necessitating an echocardiogram require Medical Monitor review.Investigators should consider whether the potential benefits of treatment outweighthe potential risks in patients with cardiovascular risk factors such as confirmedarterial hypertension.

• Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limitreference ranges after a recommended ≥ 4 hour fast, at Screening

• Estimated glomerular filtration rate ≤ 35 mL/min/1.73 m2 at Screening

• Prior treatment with growth hormone, denosumab, anti-sclerostin antibody, or otheranabolic or anti-resorptive medications impacting the bone (other thanbisphosphonates) at any time

• History of external radiation therapy

• Known hypersensitivity to setrusumab or its excipients that, in the judgment of theInvestigator, places the subject at increased risk for adverse effects

• Presence or history of any condition that, in the view of the Investigator, wouldinterfere with participation, pose undue risk, or would confound interpretation ofresults

• Use of any investigational product or investigational medical device within 4 weeksor 5 half-lives (whichever is longer) of investigational drug prior to Screening, orduring the study (per discretion of the Investigator in consultation with theMedical Monitor)

• Concurrent participation in another clinical study without prior approval from thestudy Medical Monitor

• Pregnant or nursing