A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria

Inclusion Criteria:

• Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by pastmedical history of at least 2 blood Phe measurements ≥600 μmol/L.

• 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.

• Males who are sexually active with women of childbearing potential who have not hada vasectomy must agree to use a barrier method of birth control during the study andfor up to 90 days after the last dose of study drug. Males must also refrain fromsperm donations during this time period.

• Willing to continue current diet unchanged while participating in the study (unlessspecifically instructed to change diet during the study by the investigator).

Exclusion Criteria:

• Inability to tolerate oral medication.

• A female who is pregnant or breastfeeding, or considering pregnancy.

• Serious neuropsychiatric illness (for example, major depression) not currently undermedical control, that in the opinion of the investigator or PTC, would interferewith the participant's ability to participate in the study or increase the risk ofparticipation for that participant.

• Past medical history and/or evidence of renal impairment and/or condition includingmoderate/severe renal insufficiency (glomerular filtration rate [GFR] <60milliliters [mL]/minute [min] min as estimated most recently during qualifyingparticipation in a feeder study) and/or under care of a nephrologist.

• Any other condition that in the opinion of the investigator or PTC, would interferewith the participant's ability to participate in the study or increase the risk ofparticipation for that participant.

• Requirement for concomitant treatment with any drug known to inhibit folatesynthesis (for example, methotrexate).

• Concomitant treatment with tetrahydrobiopterin (BH4) supplementation (for example,sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ).

Additional criteria for non-feeder participants who did not participate in a feeder study:

• Gastrointestinal disease (such as irritable bowel syndrome, inflammatory boweldisease, chronic gastritis, and peptic ulcer disease, etc) that could affect theabsorption of study drug.

• History of gastric surgery, including Roux-en-Y gastric bypass surgery or anantrectomy 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 orsymptoms of renal disease, including calculated GFR <60 milliliters (mL)/minute/1.73square 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.