Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3)

Male and female participants were enrolled. Inclusion Criteria: 1. Age ≥ 18 years. 2. Able and willing to voluntarily complete the informed consent process. 3. Diagnosis of phenylketonuria (PKU) and failure to maintain recommended blood Phe levels on existing management (sapropterin, sepiapterin, and/or Phe-restricted diet), demonstrated by uncontrolled blood Phe level \> 360 μmol/L on current therapy any time during screening and uncontrolled blood Phe level \> 360 μmol/L on current therapy when taking the average of the 3 most recent Phe levels from the participant's medical history (inclusive of any screening values). All screening values must have been obtained more than 7 days apart, as determined by central or local laboratory. 4. Females of childbearing potential must have had a negative pregnancy test at screening and at the end of the DEP (in order to enter the RWP) and RWP (in order to enter the OLE) and been willing to have additional pregnancy tests during the study. 5. Sexually active female participants of childbearing potential must have been willing to use an acceptable method of contraception while participating in the study and for 2 weeks after the last dose. 6. Stable diet including stable medical formula regimen (if used) for at least 1 month prior to screening. 7. If using sapropterin or sepiapterin, must have been on a stable dose for at least 3 months. 8. Willing and able to continue current diet, sapropterin, sepiapterin, and large neutral amino acids unchanged during screening, DEP, and RWP and to engage in all study activities. Exclusion Criteria: 1. Currently taking Palynziq® (pegvaliase-pqpz) (within 1 month of screening). 2. Acute or chronic medical, surgical, psychiatric, or social condition or laboratory abnormality that may have increased participant risk associated with study participation, compromised adherence to study procedures and requirements, and, in the judgment of the investigator, would have made the participant inappropriate for enrollment. 3. A known or suspected diagnosis of DNAJC12 deficiency, biopterin synthesis deficiency, or irritable bowel syndrome. 4. Intolerance to or allergic reaction to Escherichia coli Nissle or any of the ingredients in SYNB1934v1 formulation, or an allergy to cinnamon. Known intolerance to proton pump inhibitors and H2 blockers, since one or the other must have been used. 5. Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 28 days prior to the first dose of SYNB1934v1 through final safety assessment in the RWP, including planned surgery, hospitalizations, dental procedures, or interventional studies that were expected to require antibiotics. Exception: topical antibiotics were allowed. 6. Pregnant, planning to become pregnant, or breastfeeding. 7. Current participation in any other investigational drug study or use of any investigational agent within 30 days or 5 half-lives (whichever was longer) prior to screening. 8. Ever received gene therapy for treatment of PKU.