Safety, Tolerability and Pharmacodynamics of SYNB1353 in Healthy Adult Volunteers

Exclusion Criteria

• •1. Acute or chronic medical, surgical, psychiatric, or social condition or laboratory abnormality that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of study safety or PD results and, in the judgment of the Investigator, would make the subject inappropriate for enrollment.
• •2. Body mass index \< 18.5 or ≥ 35 kg/m2.
• •3. History of or current immunodeficiency disorder including human immunodeficiency virus (HIV) antibody positivity.
• •4. Hepatitis B surface antigen positivity (subjects with hepatitis B surface antibody positivity and hepatitis B core antibody positivity are not excluded, provided that the hepatitis B surface antigen is negative).
• •5. Hepatitis C antibody positivity, unless a hepatitis C virus ribonucleic acid test is performed, and the result is negative.
• •6. History of febrile illness, confirmed bacteremia, or other active infection deemed clinically significant by the Investigator within 30 days prior to the anticipated first dose of IMP.
• •7. History of (within the past month) passage of 3 or more loose stools per day, where "loose stool" is defined as a Type 6 or Type 7 on the Bristol Stool Chart (see Appendix 1).
• •8. Inflammatory or irritable bowel disorder of any grade experienced within the previous 60 days.
• •9. Active or past history of GI bleeding within 60 days prior to the Screening Visit as confirmed by hospitalization-related event(s) or medical history of hematemesis or hematochezia.
• •10. Underlying cardiovascular disease or uncontrolled gastroesophageal reflux disease
• •11. Intolerance of or allergic reaction to EcN, esomeprazole and all other PPIs, or any of the ingredients in SYNB1353 or placebo formulations.
• •12. Allergy or intolerance to multiple antibiotics which would preclude use of antibiotics for eradication of SYNB1353 in case of colonization.
• •13. Currently taking or plans to take Methotrexate, Azuridine, Nitrous Oxide, Phenytoin, or Carbamazepine.
• •14. Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 28 days prior to the first anticipated dose of IMP through final assessment, including planned surgery, hospitalizations, dental procedures, or interventional studies that are expected to require antibiotics. Exception: topical antibiotics are allowed.
• •15. Major surgery (an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity) or inpatient hospital stay within the past 3 months prior to Screening.
• •16. Dependence on alcohol or drugs of abuse.
• •17. Administration or ingestion of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to the Screening Visit, or current enrollment in an investigational study.
• •18. Screening laboratory parameters (e.g., chemistry panel, hematology, coagulation) and ECG outside of the normal limits based on standard ranges or as judged to be clinically significant by the Investigator. A single repeat evaluation is acceptable.