A Long-Term Safety Study of Somavaratan in Japanese Children With Growth Hormone Deficiency

This study is a multi-center, open-label safety study assessing long-term somavaratan
administration. It is open to subjects completing a somavaratan Japanese Phase 2/3 study
(Protocol J14VR5) in children with growth hormone deficiency (GHD), as well as approximately
20 new children currently receiving daily rhGH therapy for GHD (switch subjects). For switch
subjects, the first dose of somavaratan will be administered approximately 48 hours after the
last dose of the daily rhGH. All subjects will receive somavaratan 3.5mg/kg twice-monthly.
The study will be conducted at approximately 40 medical institutions in Japan.

Inclusion Criteria:

1. Chronological Age ≥ 3.0 years.

2. Pre-pubertal status: Absent breast development in girls, testicular volume < 4.0 mL in
boys.

3. Subjects with GHD (diagnosed according to the current diagnostic guidelines) who are
receiving treatment with daily rhGH.

4. Normal thyroid function at screening visit in subjects not being treated for
hypothyroidism. Subjects requiring thyroxine replacement must be considered adequately
treated by the PI and Medical Monitor.

5. Normal adrenal function (morning cortisol and/or local stimulation test) at screening
visit or within 6 months of the screening visit, in subjects not being treated for
adrenal insufficiency. Subjects with adrenal insufficiency must receive glucocorticoid
treatment for a minimum of 4 weeks before study drug administration.

6. Pathology relating to cause of GHD must be stable for at least 6 months prior to
screening.

7. Willingness to discontinue daily rhGH therapy.

8. Legally authorized representatives must be willing and able to give informed consent

Exclusion Criteria:

- 1. Prior (in the last 12 months) or concomitant treatment with a growth promoting
agent other than rhGH [e.g., IGF-I, GH releasing hormone (GHRH), sex steroids (except
when used as primer for GH stimulation test), aromatase inhibitors and/or GnRH
agonist].

2. Current significant disease (e.g., diabetes, cystic fibrosis, renal insufficiency).
In all cases of concurrent disease, screening must be approved in writing by the
medical monitor.

3. Chromosomal aneuploidy, significant gene mutations (other than those that cause
GHD) or confirmed diagnosis of a named syndrome (e.g., Russell Silver, Prader Willi,
Turner, etc.).

4. Birth weight and/or birth length less than 5th percentile for gestational age using
local gestational age growth charts.

5. Prolonged daily (> 14 days) use of anti-inflammatory doses of oral glucocorticoids.

6. Prior history of malignancy. 7. Treatment with an investigational drug in the 30
days prior to screening. 8. Known allergy to constituents of the study drug
formulation. 9. Ocular findings suggestive of increased intracranial pressure and/or
retinopathy at screening.

10. Significant spinal abnormalities including scoliosis, kyphosis, Chiari
malformation, and spina bifida variants.

11. Significant abnormality in screening laboratory studies (as assessed by PI and
medical monitor).

12. Current social conditions which would prevent completion of study activities
(e.g., planned family move to a distant location).

13. History of pancreatitis or undiagnosed chronic abdominal pain. 14. History of
spinal or total body irradiation. 15. Presence of other pituitary hormone deficiencies
that are not properly treated.

16. Unwillingness to provide consent for participation in all trial activities