A Study of Sepiapterin in Participants With Phenylketonuria (PKU)

Key Inclusion Criteria:

For all participants:

• Women of childbearing potential must have a negative pregnancy test at screening andagree to abstinence or the use of at least one highly effective form ofcontraception for the duration of the study, and for up to 90 days after the lastdose of the study drug.

• Willing to maintain prescribed daily protein/Phe during Screening and Part 1.

• Established diagnosis of PKU with hyperphenylalaninemia (HPA) evidenced by at least 1 blood Phe measurement ≥600 micromoles (μmol)/liter (L) as documented in themedical history.

• For participants ≥1 month of age at Screening: A minimum of 1 documented blood Phemeasurement <480 μmol/L within 1 month prior to Screening.

• For participants ≥1 month of age at Screening: Two screening blood Phe concentrationvalues must be in the range ≥120 to ≤480 μmol/L.

For participants <1 month of age at the time of informed consent/assent only:

• Blood Phe at newborn screening ≥600 μmol/L.

For participants ≥30 months to <12 years of age:

• Baseline FSIQ score ≥80.

Key Exclusion Criteria:

• History of allergies or adverse reactions to any of the ingredients or excipients ofsynthetic tetrahydrobiopterin (BH4) or sepiapterin.

• Serious neuropsychiatric illness (for example, major depression) not currently undermedical control or other concurrent disease or condition that, in the opinion of theinvestigator or sponsor, would interfere with the participant's ability toparticipate in the study or increase the risk of participation for that participant.

• Treatment with BH4 supplementation (sapropterin, KUVAN) within 3 months prior toScreening.

• Current participation in another investigational drug study or use of anyinvestigational agent within 30 days prior to Screening.

• Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenicmutations in 6-pyruvoyltetrahydropterin synthase, recessiveGuanosine-5'-triphosphate (GTP) cyclohydrolase I, sepiapterin reductase, quinoiddihydropteridine reductase, or pterin 4-alphacarbinolamine dehydratase genes.

• Any clinically significant laboratory abnormality as determined by the investigator.

• Any past medical history of an abnormal physical examination and/or laboratoryfindings indicative of signs or symptoms of renal disease, including calculated (Bedside Schwartz Equation) glomerular filtration rate (GFR) <60 milliliters (mL)/minute (min)/1.73 square meter (m^2).

• Major surgery within 90 days prior to Screening visit.

Note: Other protocol-defined inclusion and exclusion criteria may apply.