Safety and Efficacy Phase 3 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children

The study will consist of a 12 month, open-label, randomized, active controlled, parallel
group study comparing the efficacy and safety of weekly MOD-4023 to daily growth hormone
(GH), Genotropin. After 12 months, subjects will have the option to enter the long term
open-label extension.

Main Study Inclusion Criteria:

1. Pre-pubertal children aged ≥3 years , and not yet 11 years for girls or not yet 12
years with either isolated GHD, or GH insufficiency as part of multiple pituitary
hormone deficiency.

2. Confirmed diagnosis of GHD by two different GH provocation tests defined as a peak
plasma GH level of ≤10 ng/mL,

3. Bone age (BA) is not older than chronological age and should be less than 10 for girls
and less than 11 for boys.

4. Without prior exposure to any r-hGH therapy (naïve patients).

5. Impaired height and height velocity defined as:

- Annualized height velocity (HV) below the 25th percentile for CA (HV < -0.7 SDS)
and gender according to sponsor calculator using Tanner, Prader, and Hermanussen

- The interval between 2 height measurements should be at least 6 months, but
should not exceed 18 months prior to inclusion

6. Baseline IGF-I level of at least 1 SD below the mean IGF-1 level standardized for age
and sex (IGF-1 SDS ≤-1)

7. Normal calculated GFR per updated bedside Schwartz formula

8. Children with multiple hormonal deficiencies must be on stable replacement therapies
(no change in dose) for other hypothalamo-pituitary-organ axes for at least 3 months
prior ICF signing

9. Normal 46XX karyotype for girls.

10. Provide consent/assent

LT-OLE Inclusion Criteria:

11. Completion of the main study (12 months of treatment) with adequate compliance.

12. Provide consent/assent

13. Agree to refrain from sexual activity

Main Study Exclusion Criteria:

1. Children with prior history of leukemia, lymphoma, sarcoma or any other forms of
cancer.

2. History of radiation therapy or chemotherapy

3. Malnourished children defined as BMI < -2 SDS for age and sex

4. Children with psychosocial dwarfism

5. Children born small for gestational age (SGA - birth weight and/or birth length <-2
SDS for gestational age)

6. Presence of anti-hGH antibodies at screening

7. Any clinically significant abnormality likely to affect growth or the ability to
evaluate growth, such as, but not limited to, chronic diseases like renal
insufficiency, spinal cord irradiation, etc.

8. T2 and T1 diabetic patients, who in the opinion of the investigator are not receiving
standard of care treatment or are non-compliant with their prescribed treatment or who
are in poor metabolic control.

9. Chromosomal abnormalities including Turner's syndrome, Laron syndrome, Noonan
syndrome, Prader-Willi syndrome, Russell-Silver syndrome, SHOX mutations/deletions and
skeletal dysplasias.

10. Concomitant administration of other treatments that may have an effect on growth such
as anabolic steroids, or sex steroids, with the exception of ADHD drugs or HRT
(thyroxin, hydrocortisone, desmopressin)

11. Children requiring glucocorticoid therapy (e.g. for asthma) that are taking
chronically a dose greater than 400 μg/d of inhaled budesonide or equivalent

12. Major medical conditions and/or presence of contraindication to r-hGH treatment.

13. More than one closed epiphyses

14. Known or suspected HIV-positive patient, or patient with advanced diseases such as
AIDS or tuberculosis.

15. Drug, substance, or alcohol abuse.

16. Known hypersensitivity to the components of study medication.

17. Other causes of short stature such as celiac disease, uncontrolled primary
hypothyroidism and rickets.

18. Possible non-compliance in respect to study conduct

19. Participation in any other trial of an investigational agent within 30 days prior to
consent

20. Study enrollment has been met or study is closed by sponsor prior to completion of
screening process.

LT-OLE Exclusion Criteria:

21. Concomitant administration of other treatments that may have an effect on growth such
as anabolic steroids, or sex steroids, with the exception of ADHD drugs or HRT
(thyroxin, hydrocortisone, desmopressin)

22. Change in medical condition during the treatment period (such as, but not limited to,
development of a serious inter-current critical illness, a severe adverse drug
reaction, etc.)

23. Positive pregnancy test

24. Unresolved drug related (Genotropin or MOD-4023) SAE from the treatment period as per
medical monitor judgement.