Efficacy and Safety of SYNB1618 and SYNB1934 in Adult Patients With Phenylketonuria

Inclusion Criteria

• •1. Age ≥ 18 years.
• •2. Able and willing to voluntarily complete the informed consent process.
• •3. Diagnosis of classic PKU based on medical history as assessed by the investigator (e.g., Phe concentration of \>1200 µmol/L at any time, low dietary Phe tolerance, or genetic diagnosis).
• •4. Blood Phe ≥ 600 µmol/L at Screening.
• •5. Stable diet including stable medical formula regimen (if used) for at least 1 month prior to Screening.
• •6. Available for and agree to all study procedures, including urine and blood collection, adherence to diet control, follow-up visits, and IMP ingestion compliance.
• •7. Male patients who are sexually abstinent or surgically sterilized (vasectomy), or those who are sexually active with a female partner(s) and agree to use an effective method of contraception (such as condom with spermicide) combined with an acceptable method of contraception for their non-pregnant female partner(s) (as defined in Inclusion Criterion #8 below) after informed consent, throughout the study, and for a minimum of 3 months after the last dose of IMP, and who do not intend to donate sperm in the period from Screening until 3 months following administration of the IMP.
• •8. Female patients who meet one of the following criteria:
• •1. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (human chorionic gonadotropin) at Screening and a negative urine pregnancy test at Baseline prior to the start of IMP and must agree to use acceptable method(s) of contraception, combined with an acceptable method of contraception for their male partner(s) (as defined in Inclusion Criterion #7 above) after informed consent, throughout the study, and for a minimum of 3 months after the last dose of IMP. Acceptable methods of contraception include hormonal contraception, hormonal or non-hormonal intrauterine device, bilateral tubal occlusion, complete abstinence, vasectomized partner with documented azoospermia 3 months after procedure, diaphragm with spermicide, cervical cap with spermicide, vaginal sponge with spermicide, or male or female condom with or without spermicide.
• •2. Premenopausal woman with one of the following:
• •i. Documented hysterectomy, ii. Documented bilateral salpingectomy, iii. Documented bilateral oophorectomy, iv. Documented tubal ligation/occlusion, v. Sexual abstinence is preferred or usual lifestyle of the patient c. Postmenopausal women (12 months or more amenorrhea verified by follicle stimulating hormone \[FSH\] assessment and over 45 years of age, in the absence of other biological or physiological causes).
• •9. Screening laboratory evaluations (e.g., chemistry panel, complete blood count \[CBC\] with differential, urinalysis, creatinine clearance, CRP) within normal limits or judged to be not clinically significant by the investigator.