STP206 for the Prevention of NEC

Protocol STP206-002 is designed as a multi-center, randomized, double-blind, placebo
controlled dose escalation study of the safety and tolerability of two doses of STP206 versus
control in four sequentially decreasing birth weight strata. The primary objective of this
study is to assess the safety and tolerability of once daily dosing of two dose levels of
STP206 versus control in four different birth weight strata in premature neonates. Secondary
objectives of this study include assessment of fecal shedding of STP206 throughout dosing and
describing the incidence of NEC, incidence of relevant clincial events (sepsis/bacteremia,
feeding intolerance, morbidity/complications of prematurity) and neonatal growth progression
in the STP206 and control treatment groups.

Neonates for whom informed consent is obtained and who meet eligibility criteria will be
eligible to enroll in this study. All neonates enrolled will receive daily doses of blinded
study treatment for between 2 and 11 weeks with the duration of dosing based upon gestational
age at birth. All neonates enrolled in the study will be placed under Universal Precautions
and all study personnel with subject contact are trained in appropriate NICU infection
control practices. While in the NICU, neonates will be evaluated daily for signs/symptoms of
NEC, feeding volumes/feeding tolerance, AEs, and concomitant medications. Physical
examinations and vital signs will be performed daily during the dosing period and at the end
of dosing/NICU discharge. Growth assessments will be performed every other week while in the
NICU and at the end of dosing/NICU discharge. Assessments for complications of prematurity,
including retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), and
bronchopulmonary dysplasia (BPD) will be performed at protocol defined timeframes. Neonates
enrolled in the study will have fecal/meconium samples collected daily through 4 days
following the start of dosing and weekly thereafter until NICU discharge to determine fecal
shedding of Bifidobacterium lactis STP6 and Lactobacillus acidophilus STP11. Following
completion of blinded study treatment dosing, neonates will be evaluated at 1 week, 4 weeks,
3 months, and 6 months for safety and growth assessments.

Neonates will be stratified into the following four birth weights: 2000-1501g, 1500 to 1000
g, 999 to 750 g and 749 to 500 g. Each birth weight stratum will contain 2 dosing groups - a
low dose STP206 group and a high dose STP206 group. Within each birth weight strata/dose
level, subjects will be randomized in a 2:1 ratio to the STP206 or control group. Enrollment
of neonates into study groups will occur sequentially. Enrollment into the high dose group
within a birth weight stratum will not proceed until after the safety data from the low dose
group is reviewed by the study independent Data Safety Monitoring Committee (DSMC).
Similarly, enrollment into the next lower birth weight stratum will not proceed until the
safety data from the high dose group of the prior weight stratum is reviewed by the study
independent Data Safety Monitoring Committee (DSMC).

Inclusion Criteria:

1. Neonates with birth weights between 2000-500g for Part A and 1500-500g for Part B

2. Ability to start treatment within four days after birth.

3. Gestational age between 23 and 32 weeks at birth

4. Obtaining of informed consent from the subject's mother after full understanding of
the study purpose and procedures.

5. Parents who agree to allow the Principal Investigator and his/her staff to follow the
procedures and assessments required by the protocol

Exclusion Criteria:

1. Infants with, or at high probability for, early onset sepsis (positive blood cultures
or with clinical/histological chorioamnionitis with the expectation of empirical
antimicrobial therapy for ≥5 days)

2. Infants with persistent pulmonary hypertension of the newborn (PPHN)

3. Congenital or chromosomal anomalies

4. Congenital or acquired gastrointestinal pathology that preclude feeds soon after birth
(e.g. cleft lip is not an exclusion criterion, but a duodenal atresia is)

5. Infants in extremis to whom no further intensive care is offered by attending
neonatologist (e.g., infant being provided only hospice/comfort care)

6. Other conditions of the infant which, in the opinion of the attending neonatologist,
preclude participation

7. Positive maternal HIV status

8. Participation in another interventional clinical trial

For Part A of the study, the following additional exclusion criterion will apply:

9. Small for gestational age neonates, i.e. neonates that weigh less that the 10th
percentile for their gestational age according to the Estimated Fetal Weight
Percentile Chart