JNT517-201 Adolescent

The goal of this Phase 2, randomized study is to assess the safety, tolerability, and pharmacokinetics (PK) of oral JNT-517 in adolescents (12 to less than 18 years of age) with PKU. Participants will receive either JNT-517 or placebo and will be blinded to their treatment assignment. Participants will have a 4 in 5 (or 80%) chance of receiving JNT-517. The study will last for up to 63 days including a Screening period, Treatment period and Follow-up period for safety.

Participants will:

• Take 75 mg JNT-517 or a placebo BID (2x per day) for 28 days

• Visit the clinic or have a mobile health nurse visit your home for checkups and tests

• Collect urine sample at home and bring to clinic on specified days

• Keep a food diary 3 days before each study visit

Key Inclusion Criteria:

1. Males and females 12 to less than 18 years of age, inclusive on Day 1.

2. Clinical diagnosis of PKU.

3. Ability to swallow tablets.

4. Average of 2 plasma Phe levels during the Screening period greater than 360 μM and no plasma Phe level less than 300 μM.

5. Body weight equal or greater than 45 kg and body mass index less than 40 kg/m2.

6. Females of childbearing potential must practice sexual abstinence or agree to use 2 highly effective contraceptive methods.

7. Capable of giving signed informed consent (emancipated minors) or parent/legal guardian to provide informed consent and the participant to give assent and confirm ability to comply with study procedures.

Key Exclusion Criteria:

1. Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.

2. Positive for hepatitis B or C or human immunodeficiency virus.

3. Any history of malignancy in the last 5 years, excluding nonmelanoma skin cancer.

4. Any history of liver disease.

5. Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.

6. Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.

7. Creatinine clearance less than 90 mL/min by Cockcroft-Gault formula.

8. History of drug or alcohol abuse in the last year

9. Current, recent, or suspected infection within 14 days of Screening of SARS CoV 2/COVID 19.

10. Participation in another investigational drug trial within 30 days or, if known 5

half-lives of investigational drug (whichever is longer).

1. Unable to tolerate oral medication.

2. Allergy to JNT-517 or any component of the investigational product.

3. Received greater than 50 mL of blood or plasma within 30 days of Screening or

greater than 500 mL of blood or plasma within 60 days of Screening.