A 104 week dose finding open label trial followed by an optional 78 week open label extension of lonapegsomatropin, a long-acting growth hormone product, administered once-a-week versus daily somatropin product in prepubertal individuals with Turner syndrome. Approximately 48 individuals (12 individuals per arm) will be randomized to receive one of three doses of lonapegsomatropin or a daily injection of somatropin. This is a trial that will be conducted in the United States.

Inclusion Criteria:

1. Age between 1 and 10 years, inclusive.

2. TS diagnosis via genetic test.

3. Prepubertal status.

4. Naïve to growth hormone therapy or growth hormone secretagogue.

5. Exhibit impaired growth defined by at least one of the following:

   1. AHV< 6 cm/year or <25ᵗʰ percentile over a time span of 6-18 months for children of 2 years and older.
   2. Height (or length for individuals < 2 years old) <10ᵗʰ percentile for sex and age according to the 2000 CDC Growth Charts for the United States.

6. Bone age within normal limits for chronological age, defined as no more than 20% above or below chronological age in months or delayed for chronological age (greater than 20% below chronological age), at screening.

7. Biochemically euthyroid (including when on thyroid hormone supplementation).

8. If on hormone replacement therapies for any hormone deficiencies other than growth hormone (e.g. adrenal, thyroid), must be on adequate and stable doses for ≥4 weeks prior to and throughout Screening.

9. Fundoscopy at Screening without signs/symptoms of intracranial hypertension or proliferative retinopathy or evidence of any other retinal disease for which growth hormone therapy is contraindicated.

10. Capable of giving signed informed consent. Participants and/or parents or legal guardians of participants must sign an informed consent statement. Assent should be obtained from all participants competent to understand the protocol, per IRB requirements.

Exclusion Criteria:

1. Turner Syndrome with presence of Y-chromosomal material on genetic testing and without a history of gonadectomy.

2. Diagnosis of diabetes mellitus.

3. Known history of clinically relevant conditions that may have an effect on growth, e.g. but not limited to celiac disease, malnutrition, treatment with potential growth-influencing medications for Attention-deficit/ hyperactivity disorder (ADHD), etc.

4. Any known, clinically significant, congenital or acquired cardiac/cardiovascular dysfunction that might interfere with growth as determined by transthoracic echocardiogram.

5. Known history or presence of malignancy.

6. Individuals with history of intracranial tumor or cysts, with evidence of growth within the last 12 months prior to Screening.

   Note - Individuals with a history of intracranial tumor may be eligible if there is no evidence of residual tumor as determined by MRI/CT scan(s) performed within 6 to 12 months prior to screening.

7. Hepatic transaminases (i.e., AST or ALT) above 3 times the upper limit of normal according to the central laboratory at screening.

8. Major medical conditions and/or presence of contraindication to hGH treatment.

9. Abnormal renal function.

10. Clinically relevant systemic illness, acute critical illness, and complications following open heart surgery, abdominal surgery, multiple accidental traumas, acute respiratory failure, or similar conditions within 6 months prior to Screening.

11. Poorly controlled hypertension.

12. Receiving prior or concurrent treatment with any agent that might influence growth or interfere with GH secretion or action such as, but not limited to, non steroidal anabolic agents, sex steroids, etc.

13. Oral/intravenous/intramuscular corticosteroids within 90 days prior to or throughout Screening.

14. Known or suspected hypersensitivity to study intervention(s) or related products.

15. Participation in any other trial involving an investigational compound within 90 days prior to Screening or in parallel to this trial.

16. Any disease or condition that, in the judgement of the investigator, may make the individual unlikely to comply with the protocol or presents undue risk.

17. Female who is pregnant, plans to be pregnant, or is breastfeeding.