• Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by past medicalhistory of at least 2 blood Phe measurements ≥600 μmol/L.
• Women of childbearing potential must have a negative pregnancy test at screening andgree to abstinence or the use of at least one highly effective form of contraceptionhe duration of the study, and for up to 90 days after the last dose of the studydrug.
• Males who are sexually active with women of childbearing potential who have not had avasectomy must agree to use a barrier method of birth control during the study and forup to 90 days after the last dose of study drug. Males must also refrain from spermdonations during this time period.
• Willing to continue current diet unchanged while participating in the study (unlessy instructed to change diet during the study by the investigator).

• Inability to tolerate oral medication.
• A female who is pregnant or breastfeeding, or considering pregnancy.
• Serious neuropsychiatric illness (for example, major depression) not currently underdical control, that in the opinion of the investigator or sponsor, would interferewith the participant's ability to participate in the study or increase the risk ofhat participant.
• Past medical history and/or evidence of renal impairment and/or condition includingderate/severe renal insufficiency (glomerular filtration rate [GFR] <60 milliliters[mL]/minute [min] min as estimated most recently during qualifying participation in ader study) and/or under care of a nephrologist.
• Any other condition that in the opinion of the investigator or sponsor, wouldwith the participant's ability to participate in the study or increase thek of participation for that participant.
• Requirement for concomitant treatment with any drug known to inhibit folate synthesis(for example, methotrexate).
• Concomitant treatment with tetrahydrobiopterin (BH4) supplementation (for example,dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ).

• Gastrointestinal disease (such as irritable bowel syndrome, inflammatory boweldisease, chronic gastritis, and peptic ulcer disease, etc) that could affect thebsorption of study drug.
• History of gastric surgery, including Roux-en-Y gastric bypass surgery or any with vagotomy, or gastrectomy.
• History of allergies or adverse reactions to synthetic BH4 or sepiapterin.
• Any clinically significant laboratory abnormality as determined by the investigator.
• Any abnormal physical examination and/or laboratory findings indicative of signs orymptoms of renal disease, including calculated GFR <60 milliliters (mL)/minute/1.73quare meter (m^2).

        Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic
        mutations in 6-pyruvoyltetrahydropterin synthase, recessive GTP cyclohydrolase I,
        sepiapterin reductase, quinoid dihydropteridine reductase, or pterin-4-alphacarbinolamine
        dehydratase genes.