Safety and Tolerability of SYNB1618 in Healthy Adult Volunteers and Adult Subjects With Phenylketonuria

This study is evaluating the safety, tolerability, kinetics, and pharmacodynamics of SYNB1618 within the following 2 study parts: Part 1 comprises a single-ascending dose (SAD) study conducted over 4 days in HV male and female subjects in up to 6 dose cohorts (3 treated:1 placebo) to identify the maximum tolerated dose (MTD) within the single-dose range studied. Up to 24 HV subjects are planned for enrollment in this part of the study. Following attainment of the MTD in HV, a SAD cohort of up to 4 subjects (male and female, ≥ 18 years old) previously diagnosed with PKU will be enrolled (3 treated:1 placebo). Part 2 comprises a multiple-ascending dose (MAD) study conducted in an inpatient setting (6 treated:2 placebo) over 10 days in HV male and female subjects in up to 4 cohorts at doses not exceeding the MTD from the SAD part of the study to identify the MTD of SYNB1618 within the multiple-dose range studied. Up to 32 HV subjects are planned for enrollment in this part of the study. Once the highest MAD cohort and the SAD PKU cohort are completed, a multiple-dose cohort of male and female subjects (≥ 18 years old) previously diagnosed with PKU are evaluated. Up to 20 subjects with PKU are planned for enrollment in the MAD PKU cohort (12 treated:8 placebo).