Efficacy and Safety of Orally Administered Engineered Probiotics (CBT102-A) for the Treatment of Children With Phenylketonuria

Inclusion Criteria:

• Blood phe ≥ 600μmol/L at newborn screening;

• Blood phe ≥ 600μmol/L at least 3 times in the last 1 year before screening, and theblood Phe ≥ 600μmol/L in the last 1 time;

• Screening laboratory evaluations (e.g., chemistry panel, complete blood count,urinalysis, creatinine clearance, CRP) within normal limits or judged to be notclinically significant by the investigator;

• Stable diet for at least 60 days prior to screening;

• Able to produce at least 2 bowel movements per week on average without using anyform of laxatives;

• Adolescents and children's guardians can voluntarily complete the whole process ofinformed consent, including stool, urine and blood collection, adherence to dietcontrol, hospital monitoring, follow-up and oral trial drug compliance, and signinformed consent.

Exclusion Criteria:

• The standard percentile values of height and weight of Chinese children aged 0 to 18years were evaluated with weight less than P3 or weight greater than P97；

• History of active or chronic passage of 3 or more loose stools per day；

• Have any medical conditions or medications that may affect the absorption ofmedications or nutrients；

• History of or current immunodeficiency disorder including autoimmune disorders；

• Subjects with obvious influenza-like symptoms caused by COVID-19 or other viralinfections during screening；

• Hepatitis B surface antigen and/or hepatitis C antibodies and/or treponema pallidumantibodies positive；

• Subjects who are dependent on drugs and alcohol；

• Received gene therapy related to PKU；

• Intolerant or allergic to Escherichia coli Nissle 1917 (EcN)；

• Active gastrointestinal bleeding or a proven history of gastrointestinal bleedingwithin 60 days prior to screening；

• Antibiotics within 28 days before the planned first dose of investigational product (IP), or anticipated during the study period；

• Take probiotic supplements within 28 days before the planned first dose of IP, oranticipated during the study period；

• A history of fever, confirmed bacteremia, or other active infection within 30 daysprior to the planned first dose of IP；

• Drugs that use of the digestive system has been used within 30 days prior to theplanned first dose of IP;

• Drugs that may affect gastrointestinal function has been used within 30 days priorto the planned first dose of IP;

• Major survery performed within 90 days before the anticipated first dose of IP orplanned surgery or hospitalization during the study period；

• Take sapropterin (KUVAN®) within 1 week before the planned first dose of IP；

• Use pegylated recombinant phenylalanine ammonia lyase (PALYNZIQ™) within 30 daysbefore the planned first dose of IP；

• History of severe immune adverse reactions to PALYZIQ；

• Participated in an interventional clinical trial and used the investigational drugwithin 60 days or 5 half-lives before the planned first dose of IP；

• Subjects who may not be able to complete the study for other reasons.