A Phase Ib Randomized, Placebo Controlled Study of the Safety and Efficacy of Once Daily Dosing of STP206 in Premature Very Low Birth Weight and Extremely Low Birth Weight Neonates
Phase: PHASE1
Conditions: Necrotizing Enterocolitis
Sponsor: Leadiant Biosciences, Inc.

Clinical Research Protocol Approval for Study STP206-002 
July 08, 2018 
 
A Phase Ib Randomized, Placebo Controlled Study of the Safety and Efficacy of Once Daily 
Dosing of STP206 in Premature Very Low Birth Weight and Extremely Low Birth Weight 
Neonates 
 
NCT01954017 
 
 

 
 
 
 
 
 
 
 
 
CLINICAL RESEARCH PROTOCOL 
 
Sponsor: 
Leadiant Biosciences, Inc. 
9841 Washingtonian Blvd.  
Suite 500 
Gaithersburg, Maryland 20878 
(800) 447-0169 
 
IND Number:  
BB 14,046 
 
Protocol Number:  STP206-002 
 
Phase: 
Ib 
 
Protocol Title:  
A Phase Ib Randomized, Placebo Controlled Study of the 
Safety and Efficacy of Once Daily Dosing of STP206 in 
Premature Very Low Birth Weight and Extremely Low Birth 
Weight Neonates  
 
Version Number:  3.0 
 
 
Amendment No.:  Amendment 2 
 
Date: 
July 08, 2018 
 
 
STATEMENT OF CONFIDENTIALITY AND RESTRICTED DISTRIBUTION 
The information contained in this document, particularly unpublished data, is the property or 
under control of Leadiant Biosciences, Inc., and is provided to you in confidence as an 
Investigator, potential Investigator, or consultant, for review by you, your staff, and an applicable 
Institutional Review Board or Independent Ethics Committee.  The information is only to be used 
by you in connection with authorized clinical studies of the investigational drug described in the 
protocol.  You will not disclose any of the information to others without written authorization from 
Leadiant Biosciences, Inc., except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered.

Leadiant Biosciences, Inc. 
Protocol STP206-002, Amendment 2 
 
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1. 
TABLE OF CONTENTS 
1. 
Table of Contents .......................................................................................................... 3 
2. 
Study Synopsis .............................................................................................................. 8 
3. 
List of Abbreviations .................................................................................................. 12 
4. 
General Study Information ......................................................................................... 14 
5. 
Introduction ................................................................................................................. 15 
5.1. 
Disease Background ............................................................................................ 15 
5.2. 
Description of Investigational Product ................................................................ 15 
5.3. 
Investigational Product Background Information ............................................... 15 
5.3.1. 
Non-Clinical Studies ........................................................................................ 15 
5.3.2. 
Clinical Studies ................................................................................................ 16 
5.3.2.1. 
Phase 1 Study in Healthy Adult Volunteers ............................................. 16 
5.3.2.2. 
Probiotics for the Prevention of NEC ....................................................... 17 
5.4. 
Target Population and Study Rationale ............................................................... 18 
5.5. 
Potential Risks and Benefits ................................................................................ 18 
6. 
Study Purpose, Objectives, and Endpoints ................................................................. 19 
6.1. 
Purpose ................................................................................................................ 19 
6.2. 
Objectives ............................................................................................................ 19 
6.2.1. 
Primary Objective ............................................................................................ 19 
6.2.2. 
Secondary Objectives....................................................................................... 19 
6.3. 
Endpoints ............................................................................................................. 19 
6.3.1. 
Primary Endpoints ........................................................................................... 19 
6.3.2. 
Secondary Endpoints ....................................................................................... 19 
6.3.2.1. 
Exploratory Endpoints .............................................................................. 20 
7. 
Study Design ............................................................................................................... 20 
7.1. 
Overview of Study Design .................................................................................. 20 
7.1.1. 
Stopping Criteria .............................................................................................. 22 
7.1.2. 
Study Periods ................................................................................................... 22 
7.1.3. 
Recruitment and Enrollment ............................................................................ 22 
7.1.3.1. 
Recruitment Definitions ........................................................................... 23 
7.2. 
Study Treatments ................................................................................................. 23 
7.2.1. 
Rationale for Dose Selection and Choice of Control Groups .......................... 23 
7.3. 
Assignment of Subjects to Treatment .................................................................. 24 
7.4. 
Study Duration ..................................................................................................... 25 
7.4.1. 
Duration of Treatment and Subject Participation ............................................ 25 
7.5. 
Methods Used to Minimize Bias ......................................................................... 25 
7.6. 
Appropriateness of Study Measurements ............................................................ 25 
7.7. 
Study Monitoring Committees ............................................................................ 26 
8. 
Study Drug and Treatments ........................................................................................ 26 
8.1. 
Description of Study Drug(s) .............................................................................. 26 
8.1.1. 
STP206 ............................................................................................................. 26 
8.1.2. 
Control ............................................................................................................. 26 
8.2. 
Supply and Labeling ............................................................................................ 26 
8.2.1. 
How Supplied................................................................................................... 26 
8.2.1.1. 
STP206 ..................................................................................................... 26 

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8.2.1.2. 
Control / Vehicle ...................................................................................... 27 
8.2.2. 
Labeling ........................................................................................................... 27 
8.3. 
Storage Conditions .............................................................................................. 28 
8.3.1. 
STP206 ............................................................................................................. 28 
8.4. 
Preparation for Administration ............................................................................ 29 
8.4.1. 
STP206 ............................................................................................................. 29 
8.4.2. 
Control ............................................................................................................. 29 
8.5. 
Study Drug Accountability .................................................................................. 29 
9. 
Study Population ......................................................................................................... 30 
9.1. 
Number of Subjects ............................................................................................. 30 
9.2. 
Inclusion Criteria ................................................................................................. 30 
9.3. 
Exclusion Criteria ................................................................................................ 30 
9.4. 
Post-Enrollment Restrictions ............................................................................... 31 
9.4.1. 
Concomitant Medications ................................................................................ 31 
9.4.2. 
Concurrent Treatments..................................................................................... 31 
9.4.3. 
Dietary Restrictions ......................................................................................... 31 
9.5. 
Withdrawal of Enrolled Subjects ......................................................................... 31 
9.5.1. 
Withdrawal Criteria ......................................................................................... 31 
9.5.2. 
Withdrawal Procedures .................................................................................... 32 
9.5.3. 
Replacement of Discontinued Subjects ........................................................... 32 
10. 
Description of Study Procedures ................................................................................ 32 
10.1. 
Informed Consent ................................................................................................ 32 
10.2. 
History and Baseline Characteristics ................................................................... 32 
10.3. 
Safety Procedures ................................................................................................ 33 
10.3.1. Physical Examination....................................................................................... 33 
10.3.2. Vital Signs ........................................................................................................ 33 
10.3.3. Growth Assessments ........................................................................................ 34 
10.3.4. Imaging Examination ....................................................................................... 34 
10.3.5. Adverse Event Assessment .............................................................................. 34 
10.3.5.1. 
Assessment and Treatment of Sepsis........................................................ 35 
10.3.5.2. 
Assessment and Treatment of Other Infections ........................................ 36 
10.4. 
Fecal Sample Collection ...................................................................................... 36 
10.5. 
Clinical Event Assessments ................................................................................. 37 
10.5.1. Feeding Tolerance ............................................................................................ 37 
10.5.1.1. 
Management of Feeding Intolerance ........................................................ 37 
10.5.2. Relevant Neonatal Morbidities/Complications of Prematurity........................ 38 
10.5.2.1. 
Necrotizing Enterocolitis .......................................................................... 38 
10.5.2.2. 
Retinopathy of Prematurity ...................................................................... 38 
10.5.2.3. 
Bronchopulmonary Dysplasia .................................................................. 38 
10.5.2.4. 
Intraventricular Hemorrhage .................................................................... 38 
10.5.2.5. 
Other Complications of Prematurity ......................................................... 38 
10.6. 
Clinical Management ........................................................................................... 39 
10.6.1. Dietary Management ........................................................................................ 39 
10.6.2. Prophylactic Treatments .................................................................................. 39 
10.6.3. Cardiovascular Monitoring and Management ................................................. 39 
10.6.4. Respiratory Monitoring and Ventilatory Management .................................... 39 

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10.7. 
Pharmacokinetic and Pharmacodynamic Assessments ....................................... 40 
10.7.1. Pharmacokinetic Assessments ......................................................................... 40 
10.7.2. Pharmacodynamic Assessments ...................................................................... 40 
10.8. 
Study Medication Administration and Compliance ............................................ 40 
10.8.1. Dosage and Administration.............................................................................. 40 
10.8.2. Suspension of Study Drug Administration ...................................................... 40 
10.8.3. Dose Adjustments ............................................................................................ 41 
10.8.4. Assessment of Study Medication Compliance ................................................ 41 
10.9. 
Recording of Concomitant Medications .............................................................. 41 
10.10. 
Compliance .......................................................................................................... 41 
11. 
Schedule of Study Procedures .................................................................................... 41 
11.1. 
Screening ............................................................................................................. 41 
11.2. 
Assessment Schedule for Complications of Prematurity .................................... 42 
11.2.1. Necrotizing Enterocolitis (NEC)...................................................................... 42 
11.2.2. Retinopathy of Prematurity (ROP) .................................................................. 42 
11.2.3. Intraventricular Hemorrhage (IVH) ................................................................. 42 
11.2.4. Bronchopulmonary Dysplasia (BPD) .............................................................. 42 
11.3. 
Dosing Period ...................................................................................................... 42 
11.3.1. Daily Assessments During Dosing .................................................................. 42 
11.3.2. Dosing Duration ............................................................................................... 43 
11.3.2.1. 
Week 1:  Day 1 (Start of Dosing) ............................................................. 43 
11.3.2.2. 
Week 1:  Days 2-7 .................................................................................... 44 
11.3.2.3. 
Week 2 ...................................................................................................... 44 
11.3.2.4. 
Week 3 ...................................................................................................... 44 
11.3.2.5. 
Week 4 ...................................................................................................... 44 
11.3.2.6. 
Weeks 5, 7, 9, and 11................................................................................ 44 
11.3.2.7. 
Weeks 6, 8 and 10..................................................................................... 45 
11.3.2.8. 
End of Dosing/Hospital Discharge ........................................................... 45 
11.3.3. Post Dosing Assessments ................................................................................. 45 
11.3.3.1. 
1 Week ...................................................................................................... 45 
11.3.3.2. 
1 Month..................................................................................................... 45 
11.3.3.3. 
3 Months ................................................................................................... 46 
11.3.3.4. 
6 Months/End of Study ............................................................................. 46 
11.4. 
Early Withdrawal Study Assessments ................................................................. 46 
12. 
Adverse Events ........................................................................................................... 47 
12.1. 
Assessment Period ............................................................................................... 47 
12.2. 
Definitions ........................................................................................................... 47 
12.2.1. Adverse Event .................................................................................................. 47 
12.2.2. Unexpected Adverse Event .............................................................................. 47 
12.2.3. Serious Adverse Event ..................................................................................... 47 
12.2.4. Relationship to Study Drug .............................................................................. 48 
12.2.5. Severity (Intensity)........................................................................................... 49 
12.3. 
Reporting Adverse Events ................................................................................... 49 
12.3.1. Reporting Complications of Prematurity ......................................................... 49 
12.4. 
Reporting Serious Adverse Events ...................................................................... 49 
12.4.1. Reporting of Other Adverse Events of Special Interest ................................... 50 

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13. 
Statistics ...................................................................................................................... 50 
13.1. 
Sample Size Determination ................................................................................. 50 
13.2. 
Statistical Methodology ....................................................................................... 50 
13.2.1. General Analysis Considerations ..................................................................... 50 
13.2.2. Analysis Populations ........................................................................................ 51 
13.2.3. Data Analysis ................................................................................................... 51 
13.2.3.1. 
Efficacy Data Analysis ............................................................................. 51 
13.2.3.2. 
Safety Data Analysis ................................................................................ 51 
13.2.3.3. 
Pharmacokinetic Data Analysis ................................................................ 51 
13.2.3.4. 
Fecal Shedding Data Analysis .................................................................. 52 
13.2.4. Handling Missing, Repeated, Unused, and Spurious Data .............................. 52 
13.2.5. Reporting of Deviations to Statistical Methodology ....................................... 52 
13.3. 
Interim Analysis .................................................................................................. 52 
13.4. 
Statistical Criteria for Termination of the Study ................................................. 52 
14. 
Administrative............................................................................................................. 52 
14.1. 
Changes to Study Protocol .................................................................................. 52 
14.1.1. Protocol Amendments ...................................................................................... 52 
14.1.2. Protocol Deviations .......................................................................................... 53 
14.2. 
Study Termination ............................................................................................... 53 
14.3. 
Ethics ................................................................................................................... 53 
14.3.1. Compliance Statement ..................................................................................... 53 
14.3.2. Institutional Review Board/Ethics Committee ................................................ 53 
14.3.3. Informed Consent............................................................................................. 54 
14.3.4. Health Insurance Portability and Accountability Act ...................................... 54 
14.3.5. Confidentiality of Subject Records .................................................................. 55 
14.3.6. Conflict of Interest ........................................................................................... 55 
14.4. 
Investigator Obligations ...................................................................................... 55 
14.5. 
Financial Disclosure ............................................................................................ 56 
14.6. 
Quality Control and Quality Assurance of Study Data ....................................... 57 
14.6.1. Monitoring and Audits ..................................................................................... 57 
14.6.2. Data Processing and Data Quality Assurance .................................................. 57 
14.7. 
Study Records ...................................................................................................... 58 
14.7.1. Regulatory Documentation .............................................................................. 58 
14.7.2. Source Documents ........................................................................................... 58 
14.7.3. Case Report Forms ........................................................................................... 59 
14.7.4. Access to Study Records .................................................................................. 59 
14.7.5. Records Retention ............................................................................................ 59 
14.8. 
Publication Policy ................................................................................................ 59 
14.9. 
Financing and Insurance ...................................................................................... 60 
15. 
Investigator Agreement ............................................................................................... 60 
16. 
References ................................................................................................................... 61 
 

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2. 
STUDY SYNOPSIS 
 
 
IND No.: BB 14,046 
Protocol No.:  
STP206-002 
Development Phase:   
I 
Indication:  
Necrotizing Enterocolitis 
Protocol Title: A Phase Ib Randomized, Placebo Controlled Study of the Safety and Efficacy of Once 
Daily Dosing of STP206 in Premature Very Low Birth Weight and Extremely Low Birth 
Weight Neonates 
Country:  
USA 
No. of centers:  
Up to 20 
Expected Study Duration: 
Approximately 55 Months 
Purpose: 
To examine the safety, tolerability, and preliminary NEC-preventative efficacy of two dose levels of 
STP206 in premature VLBW and ELBW neonates 
Study Objectives: 
Primary Objective:  
• 
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 Objective(s):  
• 
Assess the fecal shedding after daily dosing of each component of STP206 throughout the dosing phase 
• 
Describe the incidence of NEC in STP206-treated subjects compared to control subjects 
• 
Describe the incidence of clinical events (sepsis/bacteremia, feeding intolerance, 
morbidity/complications of prematurity) in STP206-treated subjects compared to control subjects 
• 
Describe the progression of standard neonatal growth parameters in STP206-treated subjects compared 
to control subjects 
Study Endpoints: 
Primary Endpoint: 
• 
The incidence and severity of adverse events (AEs), serious adverse events (SAEs), and changes in 
clinical parameters from baseline in STP206-treated subjects compared to control subjects from 
baseline through 30 days after the last dose of blinded study treatment 
Secondary Endpoints: 
• 
The incidence and the severity of AEs and SAEs in STP206-treated subjects compared to control 
subjects from baseline through six months after the last dose of blinded study treatment 
• 
The incidence of clinical events (NEC, sepsis/bacteremia, feeding intolerance, death, 
morbidity/complications of prematurity) in STP206-treated subjects compared to control subjects 
from baseline through hospital discharge 
• 
The assessment of the fecal shedding of STP206 organisms in STP206-treated subjects compared to 
its baseline and to control subjects through the last dose of  blinded study treatment 
• 
The assessment of the changes in routine clinical parameters in STP206-treated subjects compared to 
control subjects at baseline through the last dose of blinded study treatment 
• 
The assessment of the progression of standard neonatal growth parameters in STP206 treated subjects 
compared to control subjects through the 6-month postdosing visit.  
Exploratory Endpoints: 
• 
The incidence of suspected NEC (Stage I NEC) in STP206-treated subjects compared to control 
subjects through hospital discharge 
• 
The incidence of suspected sepsis in STP206-treated subjects compared to control subjects through 
hospital discharge 
• 
The incidence of antibiotic usage in STP206-treated subjects compared to control subjects through 
hospital discharge 
• 
 
Study Design and Methodology: 

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IND No.: BB 14,046 
Protocol No.:  
STP206-002 
Development Phase:   
I 
Indication:  
Necrotizing Enterocolitis 
Protocol Title: A Phase Ib Randomized, Placebo Controlled Study of the Safety and Efficacy of Once 
Daily Dosing of STP206 in Premature Very Low Birth Weight and Extremely Low Birth 
Weight Neonates 
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.  
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 
 STP6 and 
 
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).   
Sample Size: 
The study will enroll approximately 100 to 110 neonates.   
Subject Selection Criteria: 
Inclusion Criteria 
1. Neonates with birth weights between 2000-500g  
2. Ability to start treatment within four (4) days after birth 
3. Gestational age between 23 and 32 weeks at birth 
4. Obtaining of informed consent from the subject’s appropriate legally authorized representative(s) (e.g., 
one or both parents, legal guardian), as defined by local law and IRB/IEC requirements, after those 
individuals have been provided with a full understanding of the study purpose and procedures. 
5. Parent(s) 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 the expectation of 
empirical antimicrobial therapy for ≥5 days) 
2. Infants with persistent pulmonary hypertension of the newborn (PPHN) 
3. Congenital chromosomal anomalies 
4. Congenital or acquired gastrointestinal pathology that preclude feeds within 7 days 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) 

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IND No.: BB 14,046 
Protocol No.:  
STP206-002 
Development Phase:   
I 
Indication:  
Necrotizing Enterocolitis 
Protocol Title: A Phase Ib Randomized, Placebo Controlled Study of the Safety and Efficacy of Once 
Daily Dosing of STP206 in Premature Very Low Birth Weight and Extremely Low Birth 
Weight Neonates 
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 
9. Small for gestational age neonates, i.e. neonates that weigh less than the 10th percentile for their 
gestational age according to the Estimated Fetal Weight Percentile Chart in Appendix D. 
Study Duration: 
Neonates will be dosed for between 2 and 11 weeks as determined by gestational age at birth, and all 
neonates will be followed until the 6-month post dosing visit.  Thus, the total duration of study participation 
for each study subject will be between 28 and 39 weeks. 
The total duration of the study will be approximately 55 months. 
Study Drug, Dose, Route of Administration, and Duration of Treatment: 
STP206 will be dosed orally at one of two doses 
• 
STP 206 Low dose: approximately 1 billion (1x109) cfu of 
 and approximately 
100 million (1x108) cfu of 
 (total of 1.1 billion cfu) 
• 
STP206 High Dose: approximately 9 billion (9x109) cfu of 
 and approximately 
900 million (9x108) cfu of 
 (total of 9.9 billion cfu) 
Neonates will be dosed for between 2 and 11 weeks with the duration of dosing based upon gestational age 
at birth. Doses of STP206 are planned to be administered once daily, however, in neonates with dose volume 
restrictions, doses may be divided into a BID or TID schedule.  
Reference Therapy, Dose Route of Administration and Duration of Treatment: 
The control treatment will be dosed orally. 
• 
Control: matching volume of water for injection United States Pharmacopeia (USP). 
Neonates will be dosed for between 2 and 11 weeks with the duration of dosing based upon gestational age 
at birth. Doses of the control treatment are planned to be administered once daily; however, in neonates 
with dose volume restrictions, doses may be divided into a BID or TID schedule. 
Criteria for Evaluation: 
Safety Variables:    Adverse events, SAEs, and changes in clinical (physical examinations, vital signs), 
growth parameters (head circumference, body length, body weight) 
Efficacy Variables: Feeding intolerance, clinical events (NEC, sepsis/bacteremia, feeding intolerance, 
death, morbidity/complications of prematurity) 
Pharmacokinetic Variables: None 
Pharmacodynamic Variables: None 
Other Variables: Fecal shedding  
Statistical Methodology:  
Safety Variables:  
Adverse events (AEs) will be coded according to MedDRA and will be summarized in frequency tables 
displaying counts and percentages by body system, preferred term, and treatment group.   In addition, AEs 
will be summarized by relationship to study drug and by severity.  All Serious AEs will be summarized in 
a frequency table.  

Leadiant Biosciences, Inc. 
Protocol STP206-002, Amendment 2 
 
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July 08, 2018 
 
 
IND No.: BB 14,046 
Protocol No.:  
STP206-002 
Development Phase:   
I 
Indication:  
Necrotizing Enterocolitis 
Protocol Title: A Phase Ib Randomized, Placebo Controlled Study of the Safety and Efficacy of Once 
Daily Dosing of STP206 in Premature Very Low Birth Weight and Extremely Low Birth 
Weight Neonates 
Efficacy Variables: the incidence of feeding intolerance and clinical events will be compared between 
treatment groups. 
Other Variables: 
Fecal shedding 
 will be assessed by quantitative 
and/or qualitative methods and be summarized descriptively by treatment at each time point. Counts will 
be summarized as a continuous measure and will be summarized descriptively by treatment at each time 
point. Qualitative responses will be categorized and analyzed by counts and percentages and summarized 
by treatment at each time point. Change from baseline will also be summarized descriptively by treatment 
to determine whether fecal shedding values return to baseline levels. Duration of fecal shedding will be 
summarized descriptively by treatment group. 

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3. 
LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
BP 
blood pressure 
BPD 
Bronchopulmo\ 
]nary Dysplasia 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CBER 
Center for Biologics Evaluation and Research 
CRADA 
Cooperative Research and Development Agreement 
CRF 
case report form 
DCF 
data clarification form 
DGGE 
denaturing gradient gel electrophoresis  
DSMC 
data safety and monitoring committee 
DVRPA 
Division of Vaccines and Related Products Applications. 
ECG 
electrocardiogram 
FDA 
U.S. Food and Drug Administration 
G 
gram 
GCP 
good clinical practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
IEC 
independent ethics committee 
IND 
investigational new drug 
INR 
international normalized ratio 
IP 
Investigational Product 
IRB 
institutional review board 
IVH 
intraventricular hemorrhage 
LBW 
low birth weight 
LDH 
lactate dehydrogenase 
LBP 
live biotherapeutic  
µL 
microliter 
mg 
milligram 
mL 
milliliter 
MIC 
minimum inhibitory concentration 
MTD 
maximally tolerated dose 
NICHD 
National Institute of Child Health and Human Development 

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Abbreviation 
Term 
NICU 
neonatal intensive care unit 
NIH 
National Institutes of Health 
PCR 
polymerase chain reaction 
PDA 
patent ductus arteriosus 
PK 
pharmacokinetic 
Po 
per os; by mouth; oral 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
qPCR 
quantitative polymerase chain reaction 
ROP 
retinopathy of prematurity 
SAE 
serious adverse event 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SPO2 
oxygen saturation by pulse oximeter 
TPN 
total parenteral nutrition 
ULN 
upper limit of normal 
USP 
United States Pharmacopeia 

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4. 
GENERAL STUDY INFORMATION 
Sponsor Name: 
Leadiant Biosciences, Inc. 
Sponsor Address: 
9841 Washingtonian Blvd.  
Suite 500 
Gaithersburg, Maryland 20878 
(800) 447-0169 
Sponsors Authorized Representative: 
 
Vice President & Chief Medical Officer 
Leadiant Biosciences, Inc. 
9841 Washingtonian Blvd.  
Suite 500 
Gaithersburg, Maryland 20878 
Tel: 
 
Fax: 
 
Lead PI/Coordinating Investigator: 
 
 
 
 
 
 
 
 
Medical Monitor: 
 
Vice President & Chief Medical Officer 
Leadiant Biosciences, Inc. 
9841 Washingtonian Blvd.  
Suite 500 
Gaithersburg, Maryland 20878 
Tel: 
 
Fax: 
 
The following study information is contained in a study specific reference manual for this study 
protocol: 
• Participating Investigators 
• Contract Research Organization(s) 
• Central Laboratories 
• Data and Safety Monitoring Committee 

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6. 
STUDY PURPOSE, OBJECTIVES, AND ENDPOINTS 
6.1. 
Purpose 
The purpose of this study is to examine the safety, tolerability, and preliminary NEC-preventative 
efficacy of two dose levels of STP206 in premature VLBW and ELBW neonates.   
6.2. 
Objectives 
6.2.1. 
Primary Objective 
The primary objective of the 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. 
6.2.2. 
Secondary Objectives 
The secondary objectives of the study are to: 
• Assess the fecal shedding after daily dosing of each component of STP206 throughout the 
dosing phase 
• Describe the incidence of NEC in STP206-treated subjects compared to control subjects 
• Describe the incidence of clinical events (sepsis/bacteremia, feeding intolerance, 
morbidity/complications of prematurity) in STP206-treated subjects compared to control 
subjects 
• Describe the progression of standard neonatal growth parameters in STP206-treated subjects 
compared to control subjects 
6.3. 
Endpoints 
6.3.1. 
Primary Endpoints 
The incidence and severity of AEs, SAEs and changes in clinical parameters in STP206-treated 
subjects compared to control subjects from baseline through 30 days after the last dose of blinded 
study treatment. 
6.3.2. 
Secondary Endpoints 
The secondary endpoints of the study are: 
• The incidence and the severity of AEs and SAEs in STP206-treated subjects compared to 
control subjects from baseline through six months after the last dose of blinded study 
treatment 
• The incidence of clinical events (NEC, sepsis/bacteremia, feeding intolerance, death, 
morbidity/complications of prematurity) in STP206-treated subjects compared to control 
subjects from baseline through hospital discharge 
• The assessment of the fecal shedding of STP206 organisms in STP206-treated subjects 
compared to its baseline and to control subjects through the last dose of  blinded study 
treatment 

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o Study Group 2a – Birth weight 1500 to 1000 g and Low dose STP206 versus control 
o Study Group 2b – Birth weight 1500 to 1000 g and High dose STP206 versus control 
o Study Group 3a – Birth weight 999 to 750 g and Low dose STP206 versus control 
o Study Group 3b – Birth weight 999 to 750 g and High dose STP206 versus control 
o Study Group 4a – Birth weight 749 to 500 g and Low dose STP206 versus control 
o Study Group 4b – Birth weight 749 to 500 g and High dose STP206 versus control 
• Each birth weight strata/STP206 dose group will consist of 12 subjects. 
• Within each birth weight strata/STP206 dose group, subjects will be randomized in a 2:1 
ratio to either 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 DSMC. If, at any point during the study the DSMC determines that the 
high dose of STP206 is not safe and well tolerated, weight de-escalation will continue with 
the low dose of STP206.    
The sequencing of treatment groups for the study is shown in Figure 1. Enrollment will begin with 
neonates weighing 2000 - 1500 g at the low dose of STP206 (Group 1a). Safety data through the 
last dose of blinded study treatment will be evaluated by the DSMC (see Section 7.7). Subsequent 
cohorts will not open for enrollment before the data from the previous cohort has been reviewed by 
the DSMC. If the safety data review conducted by the DSMC determines there are no safety 
concerns, study groups will open sequentially as illustrated in Figure 1.   
  
Figure 1:  
Treatment Group Sequence 
 
All neonates enrolled will receive daily doses of blinded study treatment through 34 weeks of post-
conceptional age or neonatal intensive care unit (NICU) discharge, whichever comes first. 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 
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performed at protocol defined timeframes (see Section 11.2). 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 
 
(STP6) and 
 (STP11).   
Following completion of blinded study treatment dosing, neonates will be evaluated at 1 week, 
1 month, 3 months, and 6 months for safety and growth assessments. 
7.1.1. 
Stopping Criteria 
The following stopping events reported to Leadiant will be evaluated by the DSMC to assess 
whether the events merit a temporary suspension or stopping study enrollment:    
• Any death due to an AE assessed to be directly related to the administration of STP206 
• Isolation of an STP206 organism from a normally sterile site (including bacteremia but 
excluding peritonitis in association with intestinal necrosis) in any subject 
All reports of stopping events will be forwarded to the DSMC for review.  If either of the above 
events occurs, enrollment will be suspended temporarily while the DSMC is evaluating the event.  
Subjects on blinded study drug will continue dosing during the assessment of the event.   
If a stopping criterion is met, the DSMC will perform an unblinded review of the event to assess 
causality and its overall impact on subject safety and provide its recommendations to Leadiant. If 
an event, in the opinion of the DSMC, is related to the administration of STP206, dosing of all 
ongoing study subjects will be halted, and the study will be suspended temporarily. FDA will be 
notified of all DSMC’s recommendations before taking any actions with the study.  
A flow diagram for the process of evaluating infections of normally sterile sites that are suspected 
to be associated with STP206 organisms (i.e., gram positive bacilli) is provided in Appendix E. 
7.1.2. 
Study Periods 
Subject participation will be classified into four study periods: 
• Screening Period – from the time of informed consent through administration of the first 
dose of study drug. 
• Treatment Period – this will be the period when subjects are actively being administered 
blinded study treatment. 
• Immediate Follow-up Period – this period will begin the day following the last dose of 
blinded study treatment through 30 days following administration of the last dose. 
• Long-Term Follow-up Period – this period will begin after completion of the 
immediate follow-up period.  
7.1.3. 
Recruitment and Enrollment 
The total duration of recruitment for the study will be approximately 4 years. 

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The unblinded research pharmacist is responsible for maintaining treatment assignments in a secure 
place with restricted access to assure the integrity of the study blind and prevent the identity of 
treatment assignments from becoming known to blinded staff at the research facility. 
7.4. 
Study Duration 
The total duration of the study will be approximately 55 months.  
7.4.1. 
Duration of Treatment and Subject Participation 
Subjects enrolled in this study will receive a variable number of daily doses of STP206 or vehicle 
based on their gestational age. Based on the study entry criteria, treatment will be between 2 and 11 
weeks in duration determined by the subject gestational age at birth. All neonates will be followed 
the 6-month postdosing visit. 
The total duration of study participation for each study subject will be between 28 and 39 weeks. 
7.5. 
Methods Used to Minimize Bias 
Eligible study subjects for whom parental consent is obtained will be consecutively enrolled and 
randomized to receive STP206 or control using a centralized randomization system (see Section 7.3) 
in an effort to minimize subject selection bias.   
All staff performing study assessments will be blinded to the identity of the treatment assignment 
to which the infant has been randomized in an effort to minimize bias in study assessments. Fecal 
shedding results will not be shared with the study sites during the course of the study as these results 
may potentially unblind study staff to the identity of treatment. 
As study drug is supplied in open-label fashion, the study will require unblinded site personnel to 
randomize subjects and prepare study drugs for administration. The study will use a third party (e.g., 
pharmacist or other designated site personnel who has no role in screening, enrolling, or qualifying 
study subjects) blind to minimize bias in study conduct.   
As there may be a visual difference between STP206 and control treatments (white vs. clear, 
respectively), an opaque syringe will be used to administer the blinded study treatment. 
7.6. 
Appropriateness of Study Measurements 
The physical examinations and AE assessments used in this study are standard measures of 
monitoring safety during the course of clinical trials. The assessments and monitoring used to 
diagnose NEC and complications of prematurity are standard methods utilized in NICUs and are 
appropriate to assess study objectives. Growth measurements used in this study are standard for the 
determining neonatal growth.   
Fecal shedding will be monitored by validated qPCR assays developed specifically for the detection 
of the STP206 organisms in feces. 
Identification of STP206 organisms in cultures of normally sterile sites will be assessed using 
validated qPCR assays that were developed for the detection of the components of STP206 from 
isolates. 

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7.7. 
Study Monitoring Committees  
An independent DSMC will be used to review data generated in this study, provided as a separate 
document. A Charter for the DSMC outlining the membership, roles and responsibilities was 
developed and finalized prior to the initiation of the study and submitted to the FDA on 03 December 
2013 (SN 0030). 
Available data on primary and secondary endpoints, including AEs, will be included in each review. 
The DSMC can give recommendations regarding continuation of study, temporary hold on study 
while additional data is further analyzed, or termination of the study. The DSMC will also review 
events that may constitute stopping criteria (see Section 7.1.1) on an as needed basis. Unscheduled 
DSMC review of study data may occur at any time on an as-needed basis if requested by the DSMC. 
The DSMC will review data for each dose/birth weight group to assess whether proceeding to lower 
birth weight and/or higher STP206 doses is warranted. Data reviewed at each DSMC meeting will 
follow the following schedule: 
• For the first group of subjects (Study Group 1a – Birth weight 2000 to 1501 g and low dose 
STP206), data will be reviewed through the completion of dosing. 
• For the next six DSMC reviews (Study Groups 1b through 4a), data the current dose group 
will be reviewed through the completion of dosing along with 30-day post dosing data from 
the prior dose group. 
• For the final DSMC review (Study Group 4b), data through 30-days post dosing will be 
reviewed. 
8. 
STUDY DRUG AND TREATMENTS 
8.1. 
Description of Study Drug(s) 
8.1.1. 
STP206 
STP206 Live Biotherapeutic is a combination of defined quantities of lyophilized 
 
 (STP6) and 
 (STP11) components of drug product. The product 
components will be individually reconstituted with water for injection (USP) prior to administration. 
8.1.2. 
Control 
The control for this study will be water for injection (USP), the vehicle used to reconstitute STP206. 
8.2. 
Supply and Labeling 
8.2.1. 
How Supplied 
8.2.1.1. STP206 
The individual components of STP206, 
 (STP6) and 
 
 (STP11), will be supplied separately in individual 3-mL-glass vials covered with rubber 
stoppers and aluminum caps with color-coded plastic flip-tops. 

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• Each vial of STP6 contains between 5 x 108 and 5 x 1010 CFU per vial and identified with a 
white flip-top. 
• Each vial of STP11 contains between 5x107 and 5x109 CFU per vial and identified with a 
violet flip-top.   
STP6 and STP11 components of STP206 drug product will be packaged in the separate boxes 
containing 50 vials per box. 
8.2.1.2. Control / Vehicle 
Control/vehicle, i.e., water for injection (USP), will not be supplied by Leadiant; it will be provided 
by the research sites conducting the study. 
8.2.2. 
Labeling 
Each vial of the STP206 drug product will be labeled with the product component name and a viable 
cell (CFU) count per vial, Investigational use statement, and a statement cautioning the product is 
only for oral use. The vial label will also have extra space for recording of dispensing date and ID 
of the subject to whom the drug was administered. The samples of vial labels are provided in 
Figure 2. 
Figure 2:  
Sample of STP6 and STP11 Vial Labels  
 
 
 
 
 
 
 
 
Each box of 
 (STP6) and 
 (STP11) will be labeled 
with the box number, protocol number, product name, lot number, manufacture date, Investigational 
use statement, storage condition, preparation and administration instructions and manufacturer and 
sponsor information. The samples of box labels are provided in Figure 3.  
Sample Label 
 STP6 (5 x 108 to 5 x 1010 cfu/vial) 
FOR ORAL USE ONLY 
Caution:  New Drug - Limited by Federal Law to Investigational Use
 
 
Sample Label 
 STP11 (5 x 107 to 5 x 109 cfu/vial) 
FOR ORAL USE ONLY 
Caution:  New Drug - Limited by Federal Law to Investigational Use  
 

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Figure 3: 
The Box Label Samples for Components of STP206 Drug Product  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.3. 
Storage Conditions 
8.3.1. 
STP206 
The vials of individual components of STP206, 
 (STP6) and 
 
 (STP11) will be stored under monitored refrigerated conditions (2 - 8°C) prior to 
reconstitution for use in the research pharmacy at each site. 
Sample Label 
Box # [XX] 
Protocol STP206-002                                     ***FOR ORAL USE ONLY*** 
Contains 50 vials of 
 STP6 (5 x 108 to 5 x 1010 cfu/vial) 
 
Lot No. 08SBF03  
                       Date of Mfg.: 07Nov2008 
Store at 2 – 8 °C 
Caution:  New Drug - Limited by Federal Law to Investigational Use  
Reconstitute with Water for Injection and co-administer with 
 STP11 
per protocol instructions 
Manufactured by:  
 
  
Manufactured for:  Leadiant Biosciences, Inc. 
9841 Washingtonian Blvd., Suite 500 
Gaithersburg, MD 20878 
(800) 447-0169 
Sample Label 
Box # [XX] 
Protocol STP206-002                                     ***FOR ORAL USE ONLY*** 
Contains 50 vials of 
 STP11 (5 x 107 to 5 x 109 cfu/vial) 
Lot No. 09SLF01  
                       Date of Mfg.: 12Mar2009 
Store at 2 – 8 °C 
Caution:  New Drug - Limited by Federal Law to Investigational Use  
 
Reconstitute with Water for Injection and co-administer with 
 STP6 per 
protocol instructions 
 
Manufactured by:  
 
  
Manufactured for:  Leadiant Biosciences, Inc. 
9841 Washingtonian Blvd., Suite 500 
Gaithersburg, MD 20878 
(800) 447-0169 

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8.4. 
Preparation for Administration  
8.4.1. 
STP206 
Each vial of STP6 
 and STP11 
 will be 
reconstituted using with 1.0 mL of water for injection of USP quality in the research pharmacy 
(Note: STP206 must not be reconstituted at the subject’s bedside). The appropriate volume of the 
reconstituted bacterial suspension will be removed from STP6 and STP11 vials by sterile syringes 
and stored in the individual syringes until administered. The reconstituted STP206 must be 
administered within 2 hours following reconstitution. 
The following dose volumes will be administered: 
• For the low dose of STP206, 0.1 mL of STP6 and 0.1 mL STP11 will be drawn up for 
administration (0.2 mL total).    
• For the high dose of STP206, 0.9 mL of STP6 and 0.9 mL of STP11 will be drawn up for 
administration (1.8 mL total).    
The syringes with the reconstituted STP206 will be labeled with the protocol number, subject 
identification (randomization number and initials), date and time of preparation, dose volume, and 
the words “contains STP6 or vehicle” 
 or “contains STP11 or vehicle” 
 
.   
8.4.2. 
Control 
Syringes containing the matching volume of vehicle for both STP6 and STP11 will be used as the 
control.  Syringes will be labeled in the same manner as syringes with STP206 to maintain study 
blinding. 
8.5. 
Study Drug Accountability  
The Food and Drug Administration requires accounting for the disposition of all study material 
(active or control). The Investigator is responsible for ensuring that a current record of study drug 
disposition is maintained and dispensed only at an official study site by authorized personnel as 
required by applicable regulations and guidelines. Records of product disposition as required by 
federal 
law 
consist 
of 
the 
date 
received, 
date 
dispensed/administered, 
quantity 
dispensed/administered, and the subject to whom the material was administered.   
The Investigator or designee authorized by the Investigator will be responsible for maintaining 
accurate records of the shipment, dispensing/return of the study drug by the study site, and return of 
used/undispensed study drug to Leadiant. Drug accountability records must be available for 
inspection by Leadiant or its representative and is subject to inspection by a regulatory agency (e.g., 
FDA, EMA) at any time. Copies of the records will be provided to Leadiant at the conclusion of the 
study.   
At the termination of the study, all unused investigational product must be returned to Leadiant (or 
destroyed, if not feasible to return to Leadiant). A written explanation will be required for any 
product not returned to Leadiant, stating the reason it was not returned. An Investigational Product 
Return Form and the study drug accountability form must be maintained in either the pharmacy or 

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study site. Study drug accountability records will be reviewed by an unblinded monitor on a routine 
basis.   
9. 
STUDY POPULATION 
9.1. 
Number of Subjects 
The study will be conducted at up to 20 active centers. 
This study will require at least nine evaluable neonates (i.e., completing minimum dosing duration 
described in Section 11.3.2 and having a post-dosing assessment performed) per treatment group 
for each of the eight treatment groups. It is not expected that there will be a high percentage of 
neonates that do not meet evaluability criteria. Thus, to achieve the required number of evaluable 
neonates, it is anticipated that approximately 100 to 110 neonates will be enrolled in this study.   
There are no limitations on the number of subjects that may be enrolled at each center. 
9.2. 
Inclusion Criteria 
1. Neonates with birth weights between 2000-500g  
2. Ability to start treatment within four (4) days after birth. 
3. Gestational age between 23 and 32 weeks at birth. 
4. Obtaining of informed consent from the subject’s appropriate legally authorized 
representative(s) (e.g., one or both parents, legal guardian), as defined by local law and IRB/IEC 
requirements, after those individuals have been provided with a full understanding of the study 
purpose and procedures. 
5. Parent(s) who agree to allow the Principal Investigator and his/her staff to follow the procedures 
and assessments required by the protocol. 
9.3. 
Exclusion Criteria 
1. Infants with, or at high probability for, early onset sepsis (positive blood cultures or with the 
expectation of empirical antimicrobial therapy for ≥5 days). 
2. Infants with persistent pulmonary hypertension of the newborn (PPHN) 
3. Congenital chromosomal anomalies. 
4. Congenital or acquired gastrointestinal pathology that preclude feeds within 7 days 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. 

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9. Small for gestational age neonates, i.e. neonates that weigh less than the 10th percentile for their 
gestational age according to the Estimated Fetal Weight Percentile Chart in Appendix D. 
9.4. 
Post-Enrollment Restrictions 
9.4.1. 
Concomitant Medications 
Products containing probiotic bacteria are prohibited. There are no other restrictions on concomitant 
medications.  
9.4.2. 
Concurrent Treatments 
There are no restrictions on concurrent treatments other than those described under clinical 
management (Section 10.6). 
9.4.3. 
Dietary Restrictions 
Dietary management of neonates is described in Section 10.6.1.    
9.5. 
Withdrawal of Enrolled Subjects 
In the absence of a medical contraindication or significant protocol violation, every effort will be 
made by the Principal Investigator to keep subject in the study. The primary reason for a subject 
withdrawing prematurely should be selected from the following standard categories: 
• Adverse Event - clinical or laboratory events that in the judgment of the Principal 
Investigator require discontinuation of study medication in the best interests of the subject. 
• Death – death of the subject, whether study related or not. 
• Withdrawal of Consent – subject’s parents desire the subject to be withdrawn from further 
participation in the study in the absence of a medical need to withdraw determined by the 
Principal Investigator.  
• Lost to follow-up - the subject did not return for follow-up visit(s) following the completion 
of study treatment and hospital discharge despite attempts to contact the subject’s parents to 
maintain scheduled appointments. 
• Protocol Non-compliance - the subject’s participation in the study failed to meet protocol 
requirements, which had a direct impact on subject safety and evaluability of the subject’s 
data. The violation necessitated premature termination from the study. 
• Subject meets withdrawal criteria – the subject’s condition meets the criteria for withdrawal 
from the study (Section 9.5.1). 
• Other - causes of premature termination from the study other than the above (e.g., 
termination of study by Leadiant, subject relocated). 
9.5.1. 
Withdrawal Criteria 
Subjects will be withdrawn from the study if the subject meets any of the following criteria after the 
initiation of study treatment: 
• Necrotizing enterocolitis (Bell stage II or worse) 

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• Any event requiring stopping of all enteral intake for more than 7 days 
9.5.2. 
Withdrawal Procedures 
All subjects who are withdrawn from the study will have a post dosing assessment completed. All 
subjects who received blinded study treatment, with the exception of those for whom consent is 
withdrawn, will be followed for all subsequent study assessments per study protocol.   
9.5.3. 
Replacement of Discontinued Subjects 
The study will require a minimum of nine evaluable subjects per treatment group. If more than three 
subjects do not complete the minimum required duration of study treatment (see Section 11.3.2) and 
have a post dosing assessment, subsequent subjects not meeting the minimum required duration of 
study treatment and follow-up assessments will be replaced. 
10. 
DESCRIPTION OF STUDY PROCEDURES 
The Schedule of Assessments for the study is provided in Appendix A. 
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.   
10.1. 
Informed Consent 
After being provided with a full understanding of the study purpose and procedures, the subject’s 
appropriate legally authorized representative(s) (e.g., one or both parents, legal guardian) as defined 
by local law and IRB/IEC requirements will provide written informed consent and HIPAA 
authorization using the current version of the IRB-approved informed consent form and HIPAA 
authorization forms.  Consent from both parents (as opposed to only one) will be obtained, if 
required by the local IRB in accordance with IRB requirements. 
The Principal Investigator (PI) and other site personnel as assigned by the PI will be responsible for 
obtaining informed consent and HIPAA authorization after the study has been explained to the 
subject’s parents/legal guardian and all questions have been answered. The original signed consent 
form will be filed in the subject’s records in accordance with institutional policy and a copy will be 
provided to the subject’s parents/legal guardian. The consent process will be documented in the 
subject’s source documents and the Informed Consent Log supplied for the study. 
Written informed consent must be obtained prior to performing any study related procedures. 
If a protocol amendment requires revision to the informed consent form, the revised IRB-approved 
form must be used to obtain and document re-consent from the subject’s parents/legal guardian for 
all subjects currently enrolled in the study. 
For mothers below the age of consent and who are emancipated minors, state and local regulations 
will determine how informed consent and HIPAA authorization are obtained. 
10.2. 
History and Baseline Characteristics 
The following history and demographic data will be collected: 
• Maternal History and Baseline Characteristics – age, ethnicity, race, ongoing medical 
conditions, concomitant medications, fertility medications taken for this pregnancy (if 

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applicable), reproductive history, maternal smoking during pregnancy, alcohol use during 
pregnancy, and recreational drug use during pregnancy.   
• Pregnancy History and Delivery – pregnancy complications (description and dates), multiple 
gestation, gestational age/gestational week at time of delivery, type of delivery, and 
medications at delivery or around time of delivery. For cesarean section specify whether 
elective or emergent; for vaginal deliveries specify whether spontaneous, induced, forceps-
or vacuum-assisted.  
• Infant History and Baseline Characteristics – sex, race, birth date and time, 1- and 5-minute 
Apgar Scores, birth weight (g), head circumference (cm), length (cm), cord pH and base 
deficit (if obtained), birth resuscitation/stabilization support used (supplemental oxygen, 
PPV, CPAP, intubation, chest compression, epinephrine), pre-enrollment medications (e.g., 
surfactant, antibiotics), date/time of NICU admission. Birth weight will be characterized in 
relation to gestational age.35   
10.3. 
Safety Procedures 
10.3.1. 
Physical Examination 
Physical examinations will be performed that will include assessments of the following body 
systems:   
• Head, Eyes, Ears, Nose, Throat (HEENT) 
• Cardiovascular 
• Respiratory  
• Central nervous system  
• Abdomen/Gastrointestinal 
• Genitourinary 
• Musculoskeletal  
• Dermatologic/Skin 
Physical examination findings will be noted in the subject medical records. The screening and Day 1 
physical examinations will be recorded on a CRF for the subject. Subsequent physical examinations 
performed in the NICU will not be recorded on a CRF but all adverse findings meeting the definition 
of an AE (see Section 12.2.1), independent of relationship or severity, will be recorded on the CRF 
as either adverse events or complications of prematurity. 
10.3.2. 
Vital Signs 
Vitals signs will include: 
• Temperatures (˚C) - axillary or by skin probe 
• Heart rate (BPM) - measured by auscultation 
• Respiratory rate (breaths/minute) – measured by observation  

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• Blood pressure (mmHg) – measured by either non-invasive (oscillometric) or invasive 
(arterial pressure transducers) techniques  
• SpO2 (pulse oximetry in %)   
Vital signs will be noted in the subject medical records. The screening and Day 1 vital signs will be 
recorded on a CRF for the subject. If there are multiple measurements obtained as standard of care 
during these study days, the first assessments obtained after noon will be used for the study.  The 
date and time of when these assessments were obtained will be recorded. Subsequent vital signs 
performed in the NICU will not be recorded on a CRF, but all adverse findings will be recorded on 
the CRF as AEs. 
10.3.3. 
Growth Assessments 
The following assessments of growth will be collected:  
• Head circumference (cm) using standard measuring tape 
• Body length (cm) using standard measuring tape 
• Body weight (g) using digital scale  
10.3.4. 
Imaging Examination 
Cranial ultrasonography will be performed to ascertain presence/absence of intraventricular 
hemorrhage (IVH). If IVH is noted, the grade of the IVH will be recorded. 
10.3.5. 
Adverse Event Assessment 
AEs occurring in neonates will be determined based upon physical findings, functional findings, 
laboratory findings, and routine observation of the neonate.  AEs will be assessed from the time of 
initial administration of blinded study treatment through 6 months following completion of dosing 
and be recorded regardless of severity or relationship to blinded study treatment. Ongoing AEs will 
be followed by standard NICU practice until resolution or stabilization. For each AE, the following 
information will be recorded: 
• Onset date and time  
• Resolution date and time 
• Severity/intensity (see Section 12.2.5) 
• Relationship to study drug (see Section 12.2.4) 
• Serious or non-serious (see Section 12.2.3) 
• Actions taken to manage/treat the event 
• Outcome of the event - resolved, resolved with sequelae, ongoing, death 
Complications of prematurity (see Section 10.5.2) will be recorded separately and not recorded as 
AEs.  

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10.3.5.1. Assessment and Treatment of Sepsis 
The Investigator will initiate a work-up for suspected sepsis (including the involvement of either 
one of the two bacteria strains in STP206) for full evaluation, diagnosis, and treatment, if indicated 
by clinical signs and symptoms.  
In the case of suspected sepsis, the Investigator will:  
• Perform full clinical evaluation of the subject.  
• Study drug treatment will be suspended temporarily. Study drug treatment may be 
re-initiated at the discretion of the Investigator based on the subject’s clinical condition 
(see Section 10.8.2).  
• Obtain peripheral blood cultures (i.e., not through a central line) for aerobic and anaerobic 
pathogens to identify the offending pathogen(s) prior to initiating antibiotic treatment. If 
obtaining a culture prior to initiation of antibiotics is not possible, a culture should be 
collected as soon as possible following initiation of antibiotic treatment. 
• If the site’s local laboratory identifies gram positive bacilli in the blood culture, a sample of 
the isolate will be forwarded to the central laboratory for qPCR analysis to confirm, if the 
offending bacteria are 
 STP11 or 
 STP6.  
• Start treatment with antibiotics, as appropriate.   
• Clinical management, monitoring (e.g., clinical signs, vital signs, X-rays, and laboratory 
investigations) and supportive care of the subject will be based upon the treatment 
protocol(s) of the institution and the discretion of the treating physician and/or Principal 
Investigator based upon the individual subject requirements and changes in clinical status 
over time.  
• Feeding will be continued or adjusted based upon subject stability as determined by the 
treating physician and/or Principal Investigator (e.g., stable neonates may continue to be on 
enteral feeds, while infants with respiratory distress or suspected NEC will receive nothing 
by mouth (NPO) and be maintained on intravenous fluids).   
• If the initial cultures obtained were positive, obtain a repeat set of aerobic and anaerobic 
cultures to assess response to antibiotic treatment.  
The Investigator will maintain and/or obtain medical records pertaining to the management, 
treatment, and outcome of the event for the purpose of AE/SAE reporting. 
The incidence of sepsis with 
 is extremely rare and is NOT an 
anticipated event. Guidelines to the Investigator are provided in the study protocol for monitoring 
and documentation in the unlikely case the event occurs.  Any sepsis occurring during the study is 
considered an SAE (i.e., other important medical event; see Section 12.2.3) and will be reported as 
described in Section 12 of study protocol. 
If the central laboratory identifies 
 (STP11) or 
 (STP6) in the isolate provided 
from the local laboratory, the study enrollment will be halted and a DSMC meeting will be convened 
to review the case (see Appendix E). 

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10.3.5.2. Assessment and Treatment of Other Infections 
In the event an infection of a normally sterile site (other than sepsis) is suspected, the following 
guidelines for the evaluation, monitoring and treatment should be followed.  
The Investigator will: 
• Perform full clinical evaluation of the subject  
• Study drug treatment will be suspended temporarily. Study drug treatment may be 
re-initiated at the discretion of the Investigator based as the subject’s clinical condition 
(see Section 10.8.2).  
• Obtain aerobic and anaerobic cultures of the infected site to identify the offending 
pathogen(s) prior to initiating antibiotic treatment as appropriate based upon the location of 
the infection and the clinical need for cultures. If cultures are indicated, they should be 
obtained prior to initiation of antibiotics. If obtaining a culture prior to initiation of 
antibiotics is not possible, a culture should be collected as soon as possible following 
initiation of antibiotic treatment. 
• If the site’s local laboratory identifies gram positive bacilli in the culture, a sample of the 
isolate will be forwarded to the central laboratory for qPCR analysis to confirm if the 
offending bacteria are 
 (STP11) or 
 (STP6).  
• Start treatment with antibiotics, as appropriate.   
• The subject will be managed based upon the treatment protocol(s) of the institution and the 
discretion of the treating physician and/or Principal Investigator. Clinical management, 
monitoring (e.g., clinical signs, vital signs, X-rays, and laboratory investigations) and 
supportive care will be adjusted to individual subject requirements and changes in clinical 
status over time.  
• If initial site cultures were positive and if permissible, obtain a repeat set of aerobic and 
anaerobic cultures to assess response to antibiotic treatment. 
The Investigator will maintain and/or obtain medical records pertaining to the management, 
treatment, and outcome of the event for the purpose s of AE/SAE reporting. 
 
If the central laboratory identifies 
 STP11 or 
 STP6 in the isolate provided 
from the local laboratory, the study enrollment will be halted and DSMC meeting will be convened 
to review the case (see Appendix E). 
10.4. 
Fecal Sample Collection 
Fecal sampling for shedding will be performed. 
Prior to dosing, a baseline stool sample will be collected, if available, followed by collections during 
and following the completion of blinded study drug administration. Post dosing samples will be 
collected until discharge as outlined in the schedule of procedures.   
Diapers of infants will be checked at least every 6 hours per standard NICU practice. During the 
first 4 days of dosing, all fecal samples will be collected. After Day 4, samples will be collected one 

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time per week. If there are multiple samples per day, only a single sample will be collected for 
processing.  
Fecal samples will be collected, processed and shipped to a central laboratory as described in the 
study laboratory manual.   For samples that cannot be processed and frozen immediately after 
collection, the sample (diaper) may be stored under refrigerated conditions until freezing.   Freezing 
of samples must occur within 12 hours of collection.  The time of collection and freezing of the 
samples will be recorded. 
Fecal samples will be analyzed for 
 using qPCR.  
10.5. 
Clinical Event Assessments 
10.5.1. 
Feeding Tolerance  
Neonates will have feeding method (tube, bottle, or breast), feeding content (breast milk, donor milk 
or preterm formula), daily feeding volumes (for tube and bottle feeds), and presence/absence of 
feeding tolerance recorded daily. 
Neonates will have feeding tolerance evaluated by abdominal evaluation (any excessive distension 
beyond what is expected with a feed, redness of abdominal wall, firmness, presence of normal bowel 
sounds).  
Neonates who are placed on NPO status for at least 12 hours will be considered to have feeding 
intolerance. 
10.5.1.1. Management of Feeding Intolerance 
Feeding intolerance will be determined by the attending physician Investigator based on the 
evaluations in Section 10.5.1 and his/her clinical experience. 
Any subject diagnosed with feeding intolerance will have: 
• An abdominal X-ray performed to evaluate for pneumatosis intestinalis, intestinal 
perforation, and/or biliary air. 
• For subjects without the diagnosis of NEC or spontaneous intestinal perforation, 
management will be determined by the attending physician Investigator.   
• As indicated, and at the discretion of the attending physician Investigator, blood cultures and 
a CBC will be obtained. 
• The subject will be placed on NPO status for approximately 48 hours. During NPO status, 
STP206 may continue. 
• Antibiotic treatment will be initiated and continued for approximately 48 hours. 
Treatment for a time-frame less than 48 hours will not be considered a protocol violation. If, 
however, antibiotic therapy and NPO status are maintained for greater than 72 hours, the diagnosis 
of NEC will be considered.   
If NEC is diagnosed, study drug administration will be immediately discontinued. 

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10.5.2. 
Relevant Neonatal Morbidities/Complications of Prematurity  
10.5.2.1. Necrotizing Enterocolitis 
Necrotizing Enterocolitis, (see Appendix B for diagnostic and staging criteria) will be assessed 
through physical findings (abdominal distension & tenderness) and feeding tolerance. If NEC is 
suspected, an abdominal X-ray will be obtained to determine the presence of pneumatosis 
intestinalis, portal venous air, or free air. 
If NEC is diagnosed, study drug administration will be discontinued immediately. 
10.5.2.2. Retinopathy of Prematurity 
Ophthalmologic examinations are required for all preterm neonates for Retinopathy of Prematurity 
(ROP) as per NICU ROP protocols by ophthalmologists with expertise in the diagnosis of ROP, 
commonly using indirect ophthalmoscope after pupillary dilation. 
Retinopathy of Prematurity of any stage (see Appendix B for diagnostic and staging criteria) will 
be assessed through ophthalmologic examinations performed by a certified pediatric 
ophthalmologist. Ophthalmologic assessments for ROP will be performed per NICU standard 
protocols. 
10.5.2.3. Bronchopulmonary Dysplasia 
Assessments for bronchopulmonary dysplasia (BPD) will be performed per NICU standard 
protocols by the attending physician. BPD will be defined as oxygen requirement at 36 weeks post-
conceptional age to keep oxygen saturation levels above 90%. BPD will be diagnosed and assessed 
for severity, using the criteria provided in Appendix B. 
10.5.2.4. Intraventricular Hemorrhage  
Cranial ultrasound will be performed at between 5 and 7 days of age and at 28 days (±3 days) of age 
for assessment of intraventricular hemorrhage (IVH).  The Day 28 cranial ultrasound will be 
performed only if clinically indicated and the subject is still in the hospital.  If the subject is 
discharged from the hospital prior to 28 days of age or the procedure is not clinically indicated, the 
cranial ultrasound does not need to be performed.  If the 28-day procedure is not performed, the 
reason the procedure was not performed will be documented in the source document and the CRF. 
IVH will be diagnosed and graded (Grade II, III, or IV) using the criteria provided in Appendix B. 
10.5.2.5. Other Complications of Prematurity 
Study staff will evaluate neonates for the following other clinical events: 
• Spontaneous gastrointestinal perforation 
• Patent ductus arteriosus requiring treatment with indomethacin, ibuprofen or surgery  
• Late onset sepsis 
• Late onset Candida sepsis 

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10.6. 
Clinical Management 
10.6.1. 
Dietary Management  
The following guidelines are suggested for the dietary management of infants:  
• Tube vs. non-tube feeds – Tube feeds will be provided to infants who are unable to feed at 
breast or by bottle adequately, or who take prolonged duration per feeding 
(e.g. >30 minutes). 
• Content of Enteral Feeds – Enteral feeding will consist of either breast milk, donor milk or 
preterm formula. Maternal breast milk is preferred. 
• Suggested Feeding Volumes – suggested feeding volumes will be based upon birth weight 
as follows: 
o 2000 – 1501 g – starting at 20-40 mL/kg/day; increase feeds over 5-10 days to 
150 mL/kg/day 
o 1001 – 1500 g – starting at 20 mL/kg/day; increase feeds over 5-10 days to 
150 mL/kg/day 
o 500 – 1000 g – starting at 20 mL/kg/day; increase feeds over 7-15 days to 140 mL/kg/day 
• Total Parenteral Nutrition (TPN) (for infants on NPO status) – TPN will be provided under 
the discretion of the attending neonatologist.   
10.6.2. 
Prophylactic Treatments 
Neonates may be started on empiric antimicrobial therapy (e.g., ampicillin with an aminoglycoside) 
for the first 36 to 72 hours after birth per NICU procedures. If the culture at 48 hours after initiation 
of antimicrobial therapy shows “no growth, therapy should be discontinued. This empiric 
antimicrobial therapy should be discontinued once the initial blood culture is reported as “no 
growth” by 48 hours. Infants who are critically ill and considered to have clinical sepsis despite 
negative cultures may have antimicrobials continued. 
Prophylactic exogenous surfactant (e.g., Survanta, Infasurf, Curosurf) may be administered to 
subjects in this study under the discretion of the attending neonatologist. 
Indomethacin prophylaxis for intraventricular hemorrhage may be administered in accordance with 
NICU procedures for extremely low birth weight infants. (See also Appendix C for guidelines 
regarding antibiotic susceptibility.) 
10.6.3. 
Cardiovascular Monitoring and Management  
Cardiovascular status will be assessed during routine physical assessments (see Section 10.3.1).   
If cardiac problems are diagnosed, appropriate treatment will be initiated by the attending physician 
Investigator in accordance with standard NICU practice. 
10.6.4. 
Respiratory Monitoring and Ventilatory Management 
Respiratory status will be assessed during routine physical assessments by the attending physician 
Investigator using the NICU’s standard practices (see Section 10.3.1). 

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Supplemental oxygen should be administered to infants who are unable to maintain adequate oxygen 
saturation (generally considered >90%) on room air. This supplemental oxygen is normally 
provided by oxygen hood or nasal cannula. 
Infants who continue to have low oxygen saturation despite supplemental oxygen will require 
additional support, as determined by the attending physician Investigator in accordance with 
standard NICU practice. 
10.7. 
Pharmacokinetic and Pharmacodynamic Assessments 
10.7.1. 
Pharmacokinetic Assessments 
None. 
10.7.2. 
Pharmacodynamic Assessments 
None. 
10.8. 
Study Medication Administration and Compliance 
10.8.1. 
Dosage and Administration 
Dosing of blinded study drug will be initiated within 4 days (i.e., 96 hours) after birth. Dosing is 
intended to consist of a single daily bolus dose administered as part of a scheduled feeding. 
However, in neonates who are volume restricted, the total daily dose may be divided and given twice 
daily (BID) or three times daily (TID) until full amount can be tolerated in one dose. In neonates 
where the dose volume is less than the maximum volume tolerated, dosing may be supplemented 
with regular feeding. In neonates receiving continuous feeds, the feed will be interrupted for dose 
administration and then immediately restarted.  The date, time and volume of each dose 
administration will be recorded.  
In neonates who are still on tube feeds, the dose will be given by feeding tube prior to feeding. If 
dosing at the time of feeding is not possible, the dose may be given and then the line flushed with 
sterile water to assure delivery of the full dose. In larger neonates who feed orally by breast or bottle 
for all feeds and do not have a feeding tube in place, the dose will be fed directly into the mouth 
before a feed using a syringe intended for oral drug administration. In the event the dose is spit up, 
the neonate will not be re-dosed. Regurgitation of the dose will be noted in the source document and 
the case report form. 
Prior to administration, subject identification will be verified against the labeled syringes to ensure 
that the correct IP is given.   
The times of product reconstitution and dose administration will be recorded. Reconstituted 
components of STP206 should be administered within 2 hours following reconstitution. 
10.8.2. 
Suspension of Study Drug Administration 
Study drug administration will be suspended temporarily in subjects with a case of suspected sepsis 
(see Section 10.3.5.1) or infection of a normally sterile site (see Section 10.3.5.2). Study drug may 
be re-initiated at the discretion of the Investigator, if the subject’s clinical condition permits and: 
• Cultures are negative for gram positive bacilli or, 

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• STP-206 organisms are not confirmed by central laboratory analysis.  
Additionally, dosing of blinded study treatment may be withheld at the discretion of the physician 
Investigator. The reason for suspension of blinded study treatment will be documented in the 
subject’s source documents and the case report form.   
Neonates will be discontinued from the study if:  
• Dosing is suspended for greater than seven consecutive days or 
• More than two suspensions of oral dosing of five or more consecutive days each in duration 
are required. 
If the neonate is placed on NPO status for suspected NEC and the NPO status is maintained for 
greater than 24 hours, dosing of blinded study drug will be suspended until NPO status is removed. 
If NEC is diagnosed, study drug administration will be immediately discontinued. 
10.8.3. 
Dose Adjustments 
STP206 dosage adjustments will not be permitted during the study. 
10.8.4. 
Assessment of Study Medication Compliance 
All doses of blinded study drug will be administered by study staff in the NICU. Subject source 
records must document the administration of each dose of blinded study drug. 
10.9. 
Recording of Concomitant Medications 
All changes in prior and new prescription and non-prescription medications, including blood 
products, supplemental oxygen, vitamins, supplements, and vaccinations, from the start of screening 
through the 6-month post-treatment study visit are to be recorded.   
10.10. 
Compliance 
The PI and the study personnel will verify compliance with the study requirements, procedures and 
schedule of events. The PI, or physician Sub-Investigator, listed on Form FDA 1572 will be present 
for the initial administration of blinded study treatment and available for the post-dose monitoring 
and evaluation for all neonates. The PI or physician sub-investigator will be available by pager at 
all other times throughout the study for the management of the subjects enrolled in this clinical trial. 
Non-compliance with any study evaluations/procedures will be documented in the subject’s source 
documents and CRFs. 
11. 
SCHEDULE OF STUDY PROCEDURES 
11.1. 
Screening 
Parental/legal guardian informed consent must be obtained prior to performing any study 
procedures. 
The following screening procedures will be performed before the first dose of blinded study 
treatment:  
• History and baseline characteristics, including: 

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o Maternal history and baseline characteristics 
o Pregnancy history and delivery information 
o Infant history and baseline characteristics 
• Physical Examination 
• Vital Signs 
• Growth Assessment 
• Fecal sample, if produced 
• Laboratory Assessments 
o Blood Culture (from NICU admission, only if obtained per NICU standard procedures) 
• Record concomitant medications 
11.2. 
Assessment Schedule for Complications of Prematurity 
11.2.1. 
Necrotizing Enterocolitis (NEC) 
Assessments of signs and symptoms of NEC will be performed daily while the neonate is 
hospitalized. If NEC is suspected, abdominal X-rays will be performed (see Appendix B). 
11.2.2. 
Retinopathy of Prematurity (ROP) 
Retinopathy of Prematurity (ROP) of any stage (see Appendix B for diagnostic and staging criteria) 
will be assessed through ophthalmologic examinations performed by a certified pediatric 
ophthalmologist.  
Ophthalmologic assessments for ROP will be performed per NICU standard protocols. 
11.2.3. 
Intraventricular Hemorrhage (IVH) 
Cranial ultrasound will be performed at between 5 and 7 days of age and at 28 days (±3 days) of age 
for assessment of IVH.  The Day 28 cranial ultrasound will be performed only if clinically indicated 
and the patient is still in the hospital.  If the patient is discharged from the hospital prior to 28 days 
of age or the procedure is not clinically indicated, the cranial ultrasound does not need to be 
performed.  If the 28-day procedure is not performed, the reason the procedure was not performed 
will be documented in the source document and the CRF. 
11.2.4. 
Bronchopulmonary Dysplasia (BPD) 
Assessments for BPD will be performed per NICU standard protocols by the attending physician 
Investigator and defined as oxygen requirement at 36 weeks post-conception age to keep oxygen 
saturation levels above 90%. 
11.3. 
Dosing Period 
11.3.1. 
Daily Assessments During Dosing 
During the dosing period, the following assessments will be performed daily: 

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• Physical Examination and vital signs 
• Assessments of signs and symptoms of NEC  
• Assessment of AEs 
• Assessment of concomitant medication changes 
• Assessment of feeding volumes and tolerance 
11.3.2. 
Dosing Duration 
The subject’s gestational age at birth will dictate how many weeks of dosing will be administered 
as outlined in the table below. For the initial 2 weeks of daily dosing, neonates should not miss more 
than 2 doses per week. It is intended that neonates receive blinded study treatment for between 2 to 
11 weeks based upon the protocol-defined gestational age. However, in the event of early hospital 
discharge, the minimum required dosing duration is provided in Table 2. 
Table 2:  
Dosing Duration Guidelines 
Gestational Age at Birth 
Protocol Defined 
Gestational Age  
Intended Dosing 
Duration 
Weeks (Days) 
Minimum 
Required 
Cumulative Dosing 
Days a,b 
23 weeks 0/7 days to 23 weeks 6/7 days 
23 weeks 
11 (77) 
54 
24 weeks 0/7 days to 24 weeks 6/7 days 
24 weeks 
10 (70) 
49 
25 weeks 0/7 days to 25 weeks 6/7 days 
25 weeks 
9 (63) 
45 
26 weeks 0/7 days to 26 weeks 6/7 days 
26 weeks 
8 (56) 
 40 
27 weeks 0/7 days to 27 weeks 6/7 days 
27 weeks 
7 (49) 
 35 
28 weeks 0/7 days to 28 weeks 6/7 days 
28 weeks 
6 (42) 
 30 
29 weeks 0/7 days to 29 weeks 6/7 days 
29 weeks 
5 (35) 
 25 
30 weeks 0/7 days to 30 weeks 6/7 days 
30 weeks 
4 (28) 
 20 
31 weeks 0/7 days to 31 weeks 6/7 days 
31 weeks 
3 (21) 
 15 
32 weeks 0/7 days to 32 weeks 6/7 days 
32 weeks 
2 (14) 
 10 
a. 
Over the first 2 weeks of dosing, neonates should receive study drug for a minimum of 5 of the 7 dosing days, per 
week 
b. ≥70% of intended dose 
11.3.2.1. Week 1:  Day 1 (Start of Dosing) 
Subjects who pass screening evaluations and are eligible for enrollment will be randomized to study 
treatment. 
Prior to dosing, the following study procedures will be performed: 
• Physical Examination 
• Vital Signs 

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• Growth Assessment 
• Changes in concomitant medications since the screening assessment 
• Fecal sample: all fecal samples produced will be collected daily through Day 4 and then 
once weekly afterward.  
Blinded study treatment will be administered to the neonate and the time of administration recorded. 
Following the initial dose administration, the neonate will be observed continuously by a member 
of the study staff over the first 60 minutes following administration of study drug and following 
procedures will be conducted: 
• Vital signs every hour (±10 minutes) for 4 hours, then every 4 hours (± 30 minutes) through 
24 hours following dose administration  
• Physical Examination at 3 hours (±1 hour) following dose administration 
11.3.2.2. Week 1:  Days 2-7 
Subject will be dosed once per day on days 2 through 7.   
Fecal sample: All fecal samples produced will be collected daily through Day 4 and then once 
weekly afterward.   
On Day 7 (±1 day), the following procedure will be performed: 
• Growth Assessment 
11.3.2.3. Week 2 
Subject will continue to be dosed once daily on days 8 through 14.   
On day 14 (± 1 day) the following procedures will be performed: 
• Growth Assessment 
• Fecal sample 
11.3.2.4. Week 3 
Subject will continue to be dosed once daily on days 15 through 21.  
On day 21 (±1 day) the following procedures will be performed: 
• Fecal sample 
11.3.2.5. Week 4 
Subject will continue to be dosed once daily on days 22 through 28.  
On day 28 (±1 day) the following procedures will be performed: 
• Growth Assessment 
• Fecal sample 
11.3.2.6. Weeks 5, 7, 9, and 11 
Subject will continue to be dosed once daily. 

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On Days 35, 49 and 63 (±1 day) the following procedure will be performed: 
• Fecal sample 
11.3.2.7. Weeks 6, 8 and 10 
Subject will continue to be dosed once daily.   
On day 42, 56 and 70 (±1 day) the following procedures will be performed: 
• Growth Assessment 
• Fecal sample 
11.3.2.8. End of Dosing/Hospital Discharge 
Dosing will continue until a post-conception age of 34 weeks, or until hospital discharge, whichever 
comes first. If a subject stops study drug dosing prior to the post-conception age of 34 weeks, the 
following procedures will be completed on the day the subject receives his/her last dose of blinded 
study treatment: 
• Physical examination  
• Vital Signs 
• Growth Assessment 
• Fecal sample 
• Assessment of AEs 
• Assessment of concomitant medication changes 
Discharge evaluations will be performed by a physician-Investigator who is a board-certified staff 
neonatologist and be performed per standard NICU practice.  
11.3.3. 
Post Dosing Assessments 
11.3.3.1. 1 Week 
The following procedures will be performed at one week (±2 days) following completion of dosing: 
• Physical Examination 
• Vital Signs 
• Growth Assessment 
• Assessment of AEs 
• Assessment of concomitant medication changes 
11.3.3.2. 1 Month 
The following procedures will be performed between 30 to 35 days following completion of dosing: 
• Physical Examination 
• Vital Signs 

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• Growth Assessment 
• Assessment of AEs 
• Assessment of concomitant medication changes 
11.3.3.3. 3 Months 
The following procedures will be performed between 85 and 99 days following completion of 
dosing: 
• Physical Examination 
• Vital Signs 
• Growth Assessment 
• Assessment of AEs 
• Assessment of concomitant medication changes 
11.3.3.4. 6 Months/End of Study 
The following procedures will be performed between 181 and 195 days following completion of 
dosing: 
• Physical Examination 
• Vital Signs 
• Growth Assessment 
• Assessment of AEs 
• Assessment of concomitant medication changes 
11.4. 
Early Withdrawal Study Assessments  
For subjects who withdrawal from the study prior to the 6-month post-dosing follow-up, the 
following procedures will be performed: 
• Physical Examination 
• Vital Signs 
• Growth Assessment 
• Assessment of AEs 
• Assessment of concomitant medication changes 
For subjects who withdrawal from the study prior to the 6-month follow-up assessment, the 
following procedures will be performed: 
• Growth Assessment 

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12. 
ADVERSE EVENTS  
12.1. 
Assessment Period 
AEs will be assessed from the time the subject receives their initial dose of study medication through 
6 months following the last dose of study drug. All AEs reported during this period, regardless of 
severity relationship to blinded study treatment, will be recorded. 
12.2. 
Definitions 
12.2.1. 
Adverse Event   
An adverse event (AE) is any untoward medical event associated with the use of a drug in humans, 
whether or not considered drug-related.  An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding, for example), symptom, or disease temporally 
associated with the use of a drug and does not imply any judgment about causality. 
Based upon the above definition of an AE, physical examination findings/abnormalities (inclusive 
of severity, nature and duration of the finding) that, in the opinion of the principal investigator, are 
expected to be observed in this patient population would not be considered untoward medical events 
and do not require reporting as AEs. 
An untoward medical event which occurs outside the period of follow-up as defined in the protocol 
will not be considered an AE.  Worsening of a medical condition for which the efficacy of the study 
drug is being evaluated will not be considered an AE.    
12.2.2. 
Unexpected Adverse Event 
An unexpected adverse event is an AE that is not listed in the Investigator Brochure (IB) or an AE 
not listed in the IB at the specificity or severity that has been observed.  
For example, under this definition, the AE of hepatic necrosis would be considered “unexpected” 
(by virtue of greater severity) if the investigator brochure had referred previously only to elevated 
hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis 
would be considered “unexpected” (by virtue of greater specificity) if the IB listed only cerebral 
vascular accidents. “Unexpected,” as used in this definition, also refers to AEs or suspected adverse 
reactions that are mentioned in the IB as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug but are not specifically mentioned as occurring with the 
particular drug under investigation. 
12.2.3. 
Serious Adverse Event 
A serious adverse event (SAE) is an AE that in the view of either the investigator or 
sponsor, results in any of the following outcomes:  
• Results in death 
• Is life-threatening (an event that in the view of either the investigator or sponsor, its 
occurrence places the patient or subject at immediate risk of death; it does not include an 
event that had it occurred in a more severe form, might have caused death) 
• Requires in-patient hospitalization or prolongation of existing hospitalization 

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• Is a congenital anomaly or birth defect 
• Results in persistent or significant disability/incapacity or substantial disruption of the ability 
to conduct normal life functions  
• Is an important medical event 
An important medical event that may not be immediately life-threatening or result in death 
or hospitalization but based upon appropriate medical judgment, may jeopardize the patient 
or may require medical or surgical intervention to prevent one of the other outcomes listed 
above.  Examples of such events are intensive treatment in an emergency room for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; or 
development of drug dependency or drug abuse. 
The term “severe” is often used to describe the intensity (severity) of an event; the event itself may 
be of relatively minor medical significance (such as a severe headache). This is not the same as 
“serious”, which is based on subject/event outcome or action criteria usually associated with events 
that pose a threat to a subject’s life or functioning.   
In addition to the above definitions of SAEs, all occurrences of confirmed bacteremia will also be 
considered an SAE (i.e., other important medical event).   
12.2.4. 
Relationship to Study Drug 
The Investigator must attempt to determine if an AE is in some way related to the use of the study 
drug.  This relationship should be described based upon the following definitions: 
• Unrelated/Not Related: The AE is clearly due to causes distinct from the use of the study 
drug, such as a documented pre-existing condition, the subject’s clinical state, environmental 
factors, the effect of other concomitant medications or treatments administered. 
• Unlikely: The AE does not follow a reasonable temporal sequence from administration of 
the study drug, does not follow a known response pattern to the study drug, and could readily 
have been due to other causes such as the subject’s clinical state, environmental factors, the 
effect of other concomitant medications or treatments administered. 
• Possible:  The AE follows a reasonable temporal sequence from administration of the study 
drug and follows a known response pattern to the study drug, BUT, the AE could readily 
have been produced by the subject’s clinical state, environmental factors, the effect of other 
concomitant medications or treatments administered. 
• Probable: The AE follows a reasonable temporal sequence from administration of the study 
drug and follows a known response pattern to the study drug AND cannot be reasonably 
explained by the subject’s clinical state, environmental factors, the effect of other 
concomitant medications or treatments administered. The event improves upon 
discontinuation of the study drug. 
• Definite/Related:  The AE follows a reasonable temporal sequence from administration of 
the study drug and follows a known response pattern to the study drug. Based on the known 
pharmacology of the study drug, the event is clearly related to the effect of the study drug. 
The AE improves upon discontinuation of the study drug and reappears upon repeat 
exposure. 

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12.2.5. 
Severity (Intensity)  
For AEs that are quantifiable (e.g. blood pressure, lab assessments), the Investigator will assess the 
severity (intensity) of all AEs according to the following grading system: 
• Grade 1 – (Mild AE) - event does not require medical intervention 
• Grade 2 – (Moderate AE) - event is treatable with standard medical intervention 
• Grade 3 – (Severe AE) - event requires intensive medical intervention  
12.3. 
Reporting Adverse Events 
All new events, as well as those that worsen in intensity or frequency relative to baseline, which 
occur must be captured. The Investigator or his/her staff should elicit information regarding the 
occurrence of adverse events through physical examination results, review of laboratory results, 
and, if appropriate, questioning of the neonate’s parents/guardians.   
Information to be recorded for each AE includes: 
• A medical diagnosis of the event (if a medical diagnosis cannot be determined, a description 
of each sign or symptom characterizing the event should be recorded)  
• The date and time of onset of the event  
• The date and time of resolution of the event  
• Assessments of severity, causal relationship, and seriousness of the AE (see definitions in 
Sections 12.2.3, 12.2.4, and 12.2.5) 
• Action(s) taken (if any) for management of the AE 
• Outcome of the AE:  subject recovered (without sequelae); subject recovered with sequelae; 
event ongoing; subject died  
All AEs will be followed until resolution or stabilization. 
12.3.1. 
Reporting Complications of Prematurity 
Complications of prematurity will not be classified as AEs, but as study outcomes.   
12.4. 
Reporting Serious Adverse Events 
All serious events, regardless of relationship to study drug, must be reported to Leadiant as described 
below. 
• SAEs that are fatal or life–threatening must be reported to Leadiant or their designee by 
telephone immediately after site personnel first become aware of the event. Within 24 hours, 
the Leadiant Serious Adverse Event Form must be faxed to the medical monitor or designee 
regardless of whether full information regarding the event is known or not. If full information 
is not known, additional follow-up by the Investigator will be required. 
• All other SAEs must be reported to the Leadiant medical monitor or designee within 24 
hours by phone, e-mail or fax after becoming aware of the event. Within 48 hours, the 
Leadiant Serious Adverse Event Form must be faxed to the medical monitor or designee 

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regardless of whether full information regarding the event is known or not. If full information 
is not known, additional follow-up by the Investigator will be required. 
All SAE reports will be reported to a representative of Leadiant as described in the Study Reference 
Manual. 
All SAEs will be evaluated by the Leadiant medical monitor or designee.  If meeting the 
requirements for expedited reporting, Leadiant will report the AE to all regulatory authorities with 
jurisdiction over ongoing trials with the study drug and to all other investigators involved in clinical 
trials with STP206.   
The Investigator must report all SAEs, reported to regulatory authorities in an expedited manner to 
the reviewing IRB. For all other SAEs, the Investigator must report all SAEs in accordance with the 
requirements of the reviewing IRB.   
12.4.1. 
Reporting of Other Adverse Events of Special Interest  
In addition to reporting of SAEs, the following AEs that do not meet serious criteria will be reported 
to Leadiant within 48-hours using the Leadiant Serious Adverse Event Form: 
• Any discontinuation of study drug dosing due to a severe (i.e., Grade 3) AE.  These AEs will 
be reported to FDA by Leadiant. 
• Any infection confirmed to be due to 
 
that is not reported as an SAE.  Infections due to STP206 bacteria will be reported to the 
FDA by Leadiant.  
In addition, per FDA’s request during a teleconference held on 22 July 2014, blinded desk copies 
of all cases of NEC resulting in surgery or death that did not meet expedited reporting requirements 
to qualify as a 7- or 15-day IND safety report will be submitted to the FDA via a Clinical Information 
Amendment to the IND.   
13. 
STATISTICS 
13.1. 
Sample Size Determination 
The sample size for this study will not be determined statistically.   
13.2. 
Statistical Methodology  
13.2.1. 
General Analysis Considerations 
All summaries and statistical analyses will be performed using SAS, Version 9.4 or higher. 
Descriptive summaries will consist of frequencies and percentages for categorical measures and of 
the number of subjects, mean, standard deviation, median, minimum, and maximum values for 
continuous measures. Descriptive summaries will be presented for each treatment group. Any 
statistical comparisons performed on the data will be done for exploratory analysis purposes only. 

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13.2.2. 
Analysis Populations 
The safety population will be all randomized subjects who received at least one dose of blinded 
study drug. The Intent-to-treat (ITT) population will consist of all randomized subjects who received 
study medication and have at least one post-baseline evaluation. 
13.2.3. 
Data Analysis 
Details regarding the data analyses planned for the study will be outlined in the statistical analysis 
plan (SAP).  Any changes to planned methods and analyses will be described and justified in the 
SAP, as appropriate.  The SAP will be finalized prior to database lock. 
13.2.3.1. Efficacy Data Analysis 
The following efficacy parameters will be compared between those who received STP206 vs. 
control:  
• Feeding intolerance 
• Death 
• NEC incidence 
• Incidence of sepsis 
• Incidence of other neonatal complications of prematurity (ROP, IVH, BDP, etc) 
Details regarding the analysis of efficacy data will be provided in the SAP. 
13.2.3.2. Safety Data Analysis 
AEs will be assessed from the time the subject receives the initial dose of study drug through 6 
months following the last dose. AEs will be coded according to Medical Dictionary for Regulatory 
Activities (MedDRA) and summarized in frequency tables displaying counts and percentages by 
body system, preferred term, and treatment group. Subjects reporting multiple events will only be 
counted once.  
In addition, AEs will be summarized by relationship to study drug and by severity. For assessing 
relationship to study drug, any event with a study drug relationship marked as “possible”, “probable” 
or “definite/related” on the CRF will be considered related to study drug.  
All SAEs will also be summarized in a frequency table. 
Medical history (maternal, pregnancy and infant), concomitant medications, and physical 
examination findings, will also be summarized by treatment group at each timepoint where data was 
collected. 
Information on method (bottle, breast, tube) and content of feedings (formula or breast milk) will 
be summarized. 
13.2.3.3. Pharmacokinetic Data Analysis 
None. 

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13.2.3.4. Fecal Shedding Data Analysis 
Fecal shedding 
 for each treatment group 
will be assessed by quantitative and/or qualitative methods. Counts will be summarized as a 
continuous measure and will be summarized descriptively by treatment at each time point. 
Qualitative responses will be categorized and analyzed by counts and percentages and summarized 
by treatment at each time point.   
In addition, change from baseline will be calculated and summarized descriptively by treatment to 
determine whether fecal shedding values return to baseline levels. 
Duration of fecal shedding will be summarized descriptively by treatment group. 
13.2.4. 
Handling Missing, Repeated, Unused, and Spurious Data 
It is not anticipated that there will be a need to adjust for missing data in this study. All data for this 
study will be analyzed as collected on the CRF. If the need arises to account for any special 
circumstances presented by the data, details of how it will be handled will be documented in the 
SAP. 
13.2.5. 
Reporting of Deviations to Statistical Methodology 
Any deviations to the protocol defined analysis will be documented in the SAP. Deviations in 
analyses described in the SAP will be documented in the study report. 
13.3. 
Interim Analysis 
 An interim analysis is not planned. 
13.4. 
Statistical Criteria for Termination of the Study 
There are no statistical criteria for stopping the study. 
14. 
ADMINISTRATIVE 
14.1. 
Changes to Study Protocol 
14.1.1. 
Protocol Amendments 
Protocol changes must be in the form of a written amendment approved by Leadiant.   
Protocol amendments and necessary revisions to the informed consent form must be submitted by 
the Investigator to the local IRB and such amendments will only be implemented after written 
approval of the requisite IRB. Protocol changes to eliminate an immediate hazard to a study subject 
may, at the direction of Leadiant, be implemented immediately by the Investigator. The Investigator 
must then immediately inform the IRB and obtain required approvals.   
If a protocol amendment requires revision to the informed consent form, the revised IRB-approved 
form must be used to re-consent subjects currently enrolled in the study and the new form must be 
used to obtain consent from new subjects prior to enrollment. 
All amendments will be submitted to local regulatory authorities by Leadiant as required by local 
regulation. 

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14.1.2. 
Protocol Deviations  
Deviations to the protocol will not be permitted without the prior approval of Leadiant. All 
departures from this protocol will be recorded as protocol deviations, regardless of whether the 
deviation was approved by Leadiant. If Leadiant approves a protocol deviation, a written waiver 
will be provided to the Investigator. The original waiver will be filed in the site regulatory files and 
a copy filed with the study records for the subject. 
Deviations from the protocol involving informed consent, eligibility criteria, study drug 
administration, and the administration of prohibited treatments will require written IRB notification 
by the Investigator. 
14.2. 
Study Termination 
Leadiant reserves the right to temporarily or permanently discontinue the study at any site and at 
any time. Reasons for study discontinuation may include, but are not limited to, the following: 
• Investigator non-compliance with the protocol, Good Clinical Practice guidelines or 
regulatory requirements  
• Insufficient enrollment to complete the study within the prescribed timeframe 
• Safety concerns 
• Drug supply issues 
• Discontinuation of the study protocol and/or all studies with STP206 
• Request to discontinue the study by a regulatory or health authority 
Leadiant will promptly inform all Investigators and the requisite regulatory authorities, if the study 
is suspended or terminated for safety reasons. In the case of such suspension or termination, Leadiant 
will provide the Investigator with instructions regarding the disposition of subjects (e.g., termination 
of treatment, subject follow-up) currently on the study. The Investigator will promptly notify the 
IRB and implement subject disposition instructions.   
Should the study be terminated prematurely, all unused study drug(s), unused case report forms and 
any other investigational study material will be returned to the Sponsor. 
14.3. 
Ethics 
14.3.1. 
Compliance Statement 
This study will be conducted in accordance the principles of the Declaration of Helsinki, the 
International Conference on Harmonization Guidance on Good Clinical Practice and the 
requirements of federal regulatory authorities regarding the conduct of clinical trials and the 
protection of human subjects.   
14.3.2. 
Institutional Review Board/Ethics Committee  
The Investigator will submit the protocol and subsequent amendments, the Investigator’s Brochure 
and subsequent revisions, the informed consent and any other material used to inform 
subject/subjects about the study to the local IRB for approval prior to enrolling any subject/subjects 
into the study. The IRB should be duly constituted according to applicable regulatory requirements. 

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Approval must be in the form of a letter signed by the Chairperson of the IRB or the Chairperson’s 
designee, must be on IRB stationary and must include the protocol by name and/or designated 
number. IRB approval of the informed consent form must be clearly indicated in the IRB approval 
letter (indicating version/date of the version approved) or by other means utilized by the IRB (e.g., 
IRB approval stamp on the approved version of the form). If an Investigator is a member of the IRB, 
the approval letter must stipulate that the Investigator did not participate in the final vote, although 
the Investigator may participate in the discussion of the study.   
The Investigator will also report the progress of the study to the IRB on an annual basis or more 
frequently, as required by the IRB. The Investigator will also promptly inform the IRB of: 
• SAEs that the Sponsor reports to regulatory authorities in an expedited manner  
• All changes in research activity 
• Protocol deviations, as required by Leadiant or the IRB 
• Other reports, as required by the IRB 
• The completion, termination, or discontinuation of the study, and  
• A final summary of the final results at the conclusion of the study, as required by the IRB 
Copies of all correspondence between the Investigator and the IRB will be provided to Leadiant. 
14.3.3. 
Informed Consent 
The Investigator will obtain written informed consent from the subject’s appropriate legally 
authorized representative(s) (e.g., one or both parents, legal guardian), as defined by local law and 
IRB/IEC requirements, after those individuals have been provided with a full understanding of the 
study purpose, prior to performing any study-related procedures. The consent form used to 
document informed consent from study participants must contain the elements of informed consent 
as described in 21 CFR, Part 50.  
The study records (i.e., subject source documents and applicable study logs) will document that 
informed consent was obtained prior to subject participation in the study.  
14.3.4. 
Health Insurance Portability and Accountability Act 
The Investigator must obtain authorization from the subject’s mother to use and/or disclose 
protected heath information (PHI) in compliance with the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA).   
For mothers below the age of consent and who are emancipated minors, state and local regulations 
will determine how HIPAA authorization is to be obtained. 
HIPAA authorization may be obtained as part of the informed consent form or in a separate 
document and will include: 
• Identification of the parties that can use and disclose PHI 
• Identification of the parties to whom PHI may be disclosed 
• A description of the PHI 
• A description of the purpose for use and disclosure 

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• Information pertaining to the subject’s rights related to authorization 
• Information about the expiration of the authorization and how to revoke authorization 
• A statement about what may happen if authorization is not provided 
• A statement that once information has been disclosed, it may be disclosed again without 
further authorization. 
14.3.5. 
Confidentiality of Subject Records 
It is the responsibility of the Investigator to ensure that the confidentiality of all subjects 
participating in the study and all of their medical information is maintained. Case report forms and 
other documents submitted to Leadiant must not contain the name of a study participant. Each 
subject in the study will be identified by a unique identifier that will be used on all CRF’s and any 
other material submitted to Leadiant. All case report forms and any identifying information must be 
kept in a secure location with access limited to the study staff directly participating in the study.  
Personal medical information may be reviewed by representatives of Leadiant, the IRB or regulatory 
authorities in the course of monitoring the progress of the study. Every reasonable effort will be 
made to maintain such information as confidential. 
The results of the study may be presented in reports, published in scientific journals or presented at 
medical meetings; however, subject names will never be used in any reports about the study. 
14.3.6. 
Conflict of Interest  
The Investigator shall acknowledge, by signing the Investigator’s Statement/ Signature Page 
(Section 15), that the participation in this clinical study by the Investigator and his/her sub-
investigators presents no conflict of interest with the study. 
14.4. 
Investigator Obligations 
The Investigator is responsible for complying with the obligations of clinical investigators, as 
described in ICH GCP guidelines, the Declaration of Helsinki, and U.S. federal regulations as 
defined in 21 CFR Parts 50, 54, 56, and 312. These obligations include, but are not limited to, the 
following:  
1. Protect the rights, safety and welfare of subjects under the Investigator’s care. 
2. Conduct the study in accordance with the approved study protocol. 
3. Conduct the study in accordance with GCP guidelines and applicable federal, state and local 
regulations and laws. 
4. Ensure that the staff involved with the conduct of the study are knowledgeable on the study 
agents used, the study protocol, study procedures, and reporting requirements. 
5. Properly obtain informed consent and HIPAA authorization from each subject (or the subject’s 
legal representative) enrolled using the current IRB-approved forms. 
6. Supply study drug only to those subjects who are participating in the study and are under the 
direct supervision of the Investigator or an authorized sub-investigator.  The Investigator must 
not supply the study drug to any person not authorized to receive it. 

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7. Prepare and maintain accurate and complete case histories for all subjects participating in this 
trail that document all study procedures performed and record all data required for this study 
protocol. 
8. Report all SAEs to the sponsor and IRB (as necessary) within the timeframes described in this 
protocol. 
9. Report any changes in research activity and unanticipated problems involving risk to study 
participants promptly to the IRB. 
10. Report all protocol deviations promptly to Leadiant.  Significant deviations will require prompt 
notification to the IRB. 
11. Provide the IRB with copies of reports of SAEs submitted by Leadiant to regulatory authorities 
in an expedited manner (e.g., IND Safety Reports). 
12. Provide Leadiant with complete and accurate financial information to allow submission of 
complete and accurate certification and disclosure statements to FDA as required. 
It is required that either the Principal Investigator, or an appropriately delegated, licensed physician  
sub-investigator, administer or oversee the care of study subjects and review study data (e.g., AEs, 
laboratory data, treatment response data) in a timely manner. 
14.5. 
Financial Disclosure 
All Investigators and sub-investigators listed on any FDA 1572 form supplied by the Investigator 
will disclose the following information as required by 21 CFR, Part 54: 
1. Any financial arrangement entered into between Leadiant and the Investigator/sub-investigator whereby 
the value of the compensation to the Investigator/sub-investigator for conducting the study could 
be influenced by the outcome of the study. 
2. Any significant payments totaling more than $25,000 USD, exclusive of the costs of conducting 
this or other clinical studies, from Leadiant, such as a grant to fund ongoing research, 
compensation in the form of equipment, retainer for ongoing consultation, or honoraria 
3. Any proprietary interest in the test product 
4. Any significant equity interest in Leadiant Biosciences in excess of $50,000 USD 
The Investigator/sub-investigator shall promptly update financial disclosure information if any 
changes occur during the course of the study and for one year following completion of this study.  
This financial disclosure requirement includes the finances of the spouse and the dependent children 
of the Investigator/sub-investigator.  

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14.6. 
Quality Control and Quality Assurance of Study Data 
14.6.1. 
Monitoring and Audits 
During the course of the study, a clinical monitor assigned by Leadiant will make regularly 
scheduled visits to the investigational site to review the progress of the study. The frequency of 
monitoring visits will depend on the enrollment rate and performance at each site. During each visit, 
the monitor will review various aspects of the study including, but not limited to: 
• Compliance with the protocol 
• Compliance with the principles of Good Clinical Practice and regulatory requirements 
• Review of written informed consent forms for subjects enrolled  
• Comparison of source documentation to data recorded on case report forms to assure the 
completeness and accuracy of data collected 
• Continued acceptability of facilities and staff 
• Assessment of proper study drug accountability and storage 
During scheduled monitoring visits, the Investigator and the investigational site staff must be 
available to meet with the study monitor in order to discuss the progress of the study, make necessary 
corrections to case report form entries, respond to data clarification requests and respond to any 
other study-related inquiries of the monitor. 
In addition to the above, representatives of Leadiant’s auditing staff or government inspectors may 
review the conduct/results of the study at the investigational site. The Investigator must promptly 
notify Leadiant of any audit requests by regulatory authorities. The Investigator will cooperate with 
the auditor(s), make available to the auditor all requested documentation, and ensure that issues 
detected during the course of these audits are satisfactorily resolved. The Investigator will supply 
Leadiant with copies of all documentation and correspondence related to regulatory agency audits 
as outlined in the Clinical Study Agreement between Leadiant and the Investigator and/or 
Institution. If the results of the audit result in an FDA-483 (or similar document from another 
regulatory agency), the Investigator will promptly provide a copy to Leadiant and will provide a 
copy of the draft response to Leadiant prior to submission to the regulatory agency. 
14.6.2. 
Data Processing and Data Quality Assurance 
Case report forms/eCRFs will be reviewed for correctness against source document data by 
Leadiant’s monitor. If any entries into the CRF/eCRF are incorrect, incomplete or illegible, the 
monitor will request the Investigator or the study site staff to make appropriate corrections.   
Data edit and consistency checks will be applied to review for missing, out of range, or inconsistent 
data. Discrepancies will be provided to the investigational site for resolution. The discrepancy will 
be clarified by site personnel and the data corrected. 
A quality control (QC) audit of the database will be performed to assure accuracy of the database 
prior to database lock. Discrepancies noted during the audit will be corrected. Error rates determined 
during the QC audit must be within the acceptable error rate defined by the data management plan 
(DMP) prior to lock of the database. 

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14.7. 
Study Records 
The Investigator is responsible for preparing and maintaining adequate records to enable the conduct 
of the study to be documented. Study records include, but are not limited to, regulatory 
documentation (Section 14.7.1) and subject records (Sections 14.7.2 and 14.7.3). 
14.7.1. 
Regulatory Documentation 
Prior to initiating the study, the Investigator will provide Leadiant the following documents: 
•
A signed FDA Form 1572
•
A current curriculum vitae for the Principal Investigator and each sub-investigator listed on 
the FDA Form 1572
•
Copy of the current medical licenses for the Investigator and physician sub-investigators
•
Written IRB approval of the protocol, informed consent form and any other material 
provided to potential study participants with information about the study (e.g., 
advertisements)
•
A copy of the IRB-approved informed consent document and HIPAA authorization
•
Current IRB membership list for the reviewing IRB and/or multiple project assurance 
number or an IRB organization number under the Federal Wide Assurance program 
(www.ohrp.osophs.dhhs.gov)
•
A signed Investigator Protocol Agreement (see Section 15)
•
Completed financial disclosure form for the Investigator and all sub-investigators
•
Local reference laboratory documentation, including current laboratory certification, current 
laboratory normal values, and director’s CV 
During the course of the study, the Investigator will maintain current records to document regulatory 
compliance with the study including: the study protocol and amendments, all versions of the 
Investigators Brochure in effect during study conduct, signed Investigator Agreement protocol 
page(s), FDA 1572 forms, curricula vitae of the Investigator and sub-investigators, medical licenses 
of the Investigator and physician sub-investigators, financial disclosure of the Investigator and sub-
investigators, IRB approvals of the protocol, protocol amendment(s), informed consent form(s), IRB 
membership list, IRB-approved informed consent form(s), IRB correspondence, protocol 
deviations, study logs (as provided by Leadiant), drug dispensing and accountability records, safety 
reports, and all correspondence pertaining to the conduct of the study. Regulatory documentation 
will be reviewed by Leadiant or its representatives during monitoring visits to assure regulatory 
compliance.  
14.7.2. 
Source Documents 
The Investigator will maintain records separate from the case report forms in the form of clinical 
charts, medical records, original laboratory, radiology and pathology reports, pharmacy records, 
subject diary cards, etc. The Investigator will document in the clinic chart or medical record the 
name and number of the study and the date on which the subject signed informed consent prior to 
the subject’s participation in the study. Source documents must completely reflect the nature and 
extent of the subject’s medical care and must be available for verification against case report form 

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entries, when the Leadiant or its representatives visit the investigational site. All information 
obtained from source documents will be kept in strict confidentiality. 
14.7.3. 
Case Report Forms 
All site-generated study data will be entered either onto case report forms (CRFs) supplied by 
Leadiant or into an electronic Case Report Form (eCRF) via an electronic data capture (EDC) 
system. The CRFs/eCRFs are not to be used as the primary method for collection of study data 
(unless otherwise described in this section of the study protocol) and CRF/eCRF entries must be 
supported by source documents maintained by the Investigator. Only those site staff authorized at 
the initiation of the study may enter data onto the case report forms or into an EDC system.   
For studies using paper CRFs, all entries must be legible and made in black pen. If an entry error is 
made, a single line will be placed through the incorrect entry. The correct entry will then be made, 
with the correction dated and initialed by the authorized person making the entry. Any corrections 
to data entered into the CRF must be made in such a way that the original entry is not obscured. 
Resolutions to data clarification forms (DCFs) issued by Leadiant, or its designated data 
management contractor will be maintained with the CRFs for each subject. 
The Investigator is responsible for the completeness and accuracy of all CRF/eCRF data as certified 
by the Investigator’s dated signature on designated CRF/eCRF pages. 
14.7.4. 
Access to Study Records 
The Investigator will make available all records pertaining to the conduct of this study to Leadiant 
and its representatives, and auditors from domestic and foreign regulatory authorities to facilitate 
monitoring visits and study audits. 
14.7.5. 
Records Retention 
The Investigator will retain the records of the study for 2 years following the date that a marketing 
application for the study drug is approved, or if no marketing application is filed, or if such an 
application is not approved, for 2 years after the IND has been closed. Leadiant will notify 
Investigators when retention of study records is no longer required. All study records must be 
maintained in a safe and secure location that allows for timely retrieval, if needed. 
Study records that must be retained include copies of case report forms, signed informed consents, 
regulatory documentation, source documents, clinic charts, medical records, laboratory results, 
radiographic reports, and other study-specific documentation. 
Should the Investigator relocate or retire or should there be any changes in the archival arrangements 
for the study records, Leadiant must be notified. The responsibility for maintaining the study records 
may be transferred to another suitable individual, but Leadiant must be notified of the identity of 
the individual assuming responsibility for maintaining the study records and the location of their 
storage. If no other individual at the investigational site is willing to assume this responsibility, 
Leadiant will assume responsibility for maintaining the study records. 
14.8. 
Publication Policy 
Publication of study data is addressed in the Clinical Trial Research Agreement between Leadiant 
and the Investigator(s) and/or Institution(s).   

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14.9. 
Financing and Insurance 
Financing and Insurance are addressed in the Clinical Trial Research Agreement between Leadiant 
and the Investigator and/or Institution.   
15. 
INVESTIGATOR AGREEMENT 
I have reviewed Amendment 2 to Leadiant Biosciences Protocol STP206-002, entitled “A Phase Ib 
Randomized, Placebo Controlled Study of the Safety and Efficacy of Once Daily Dosing of STP206 
in Premature Very Low Birth Weight and Extremely Low Birth Weight Neonates” and agree that it 
contains all the information necessary to conduct the study as required.  I will conduct the trial in 
accordance with the principles of ICH Good Clinical Practice and the Declaration of Helsinki.   
I will maintain as confidential all written and verbal information provided to me by Leadiant 
Biosciences, including but not limited to, the protocol, case report forms, investigators’ brochure, 
material supplied at investigator meetings, minutes of teleconferences, etc.  Such material will only 
be provided as necessary to site personnel involved in the conduct of the trial, the IRB or IEC, or 
local regulatory authorities.    
I will obtain written informed consent from each prospective trial subject or each prospective trial 
subject’s legal representative prior to conducting any protocol-specified procedures.  The consent 
form used will have the approval of the local IRB or IEC. 
I will maintain adequate source documents and record all observations, treatments and procedures 
pertinent to trial subjects in their medical records.  I will accurately complete the case report forms 
supplied by Leadiant Biosciences in a timely manner.  I will ensure that my facilities and records 
will be available for inspection by representatives of Leadiant Biosciences, the local IRB or IEC or 
local regulatory authorities.  I will ensure that I and my staff are available to meet with 
representatives of Leadiant Biosciences during regularly scheduled monitoring visits. 
I will notify Leadiant Biosciences, or it’s designated representative, within 24 hours of any serious 
adverse events. Following this notification, a written report describing the SAE will be provided to 
Leadiant Biosciences, or it’s designated representative, as soon as possible, but no later than three 
days following the initial notification. 
My signature below indicates that my participation in this clinical study presents no conflict of 
interest for me or my sub-investigators with the study. 
 
 
 
 
 
 
 
 
Investigator’s Name (Print) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator’s Signature  
 
 
 
 
Date 
 
 
 

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APPENDIX A - SCHEDULE OF ASSESSMENTS 
AE=adverse event; BP=blood pressure; BPD=bronchopulmonary dysplasia; HR=heart rate; IVH=intraventricular hemorrhage; NEC=necrotizing enterocolitis; 
NICU=neonatal intensive care unit; ROP=retinopathy of prematurity; RR=respiratory rate; SpO2= pulse oximetry. 
a. 
If available. 
b. To be performed daily in NICU per standard NICU procedures, adverse findings to be recorded as AEs or complications of prematurity. 
Schedule of Events During Dosing Period 
Procedure 
Screening 
Week 1 
Day 1 
Week 1 
Days 2-4 
Week 1 
Days 5-7 
Weeks  
2, 4, 6, 8, 10 
Weeks  
3, 5, 7, 9, 11 
End of Dosing or 
Hospital 
Discharge 
Unique 
Events 
Scheduling 
Informed Consent 
x 
 
 
 
 
 
 
 
Demographics 
x 
 
 
 
 
 
 
 
Medical History (maternal) 
x 
 
 
 
 
 
 
 
Pregnancy/Delivery History (maternal) 
x 
 
 
 
 
 
 
 
Concomitant Medication history 
(maternal) 
x 
 
 
 
 
 
 
 
Medical History (infant) 
x 
 
 
 
 
 
 
 
Physical Examination  
x 
x 
b 
 
Vital Signs (Temp, BP, HR, RR, SpO2)  
x 
x 
b 
 
Growth Assessment 
x 
x 
 
x 
x 
 
x 
 
Fecal sample 
xa 
xa 
xa 
xf 
x 
x 
x 
 
Retinopathy of Prematurity (ROP)c 
 
 
 
 
 
 
 
x 
Intraventricular Hemorrhage (IVH)d 
 
 
 
x d 
xd 
 
 
 
Bronchopulmonary Dysplasia (BPD)e 
 
 
 
 
 
 
 
x 
Randomize subject 
 
x 
 
 
 
 
 
 
NEC Evaluation (daily) 
 
x 
x 
x 
x 
x 
 
 
Assessment of Feeding Volumes and 
Tolerance (daily) 
 
x 
x 
x 
x 
x 
 
 
Adverse Event Assessment (daily) 
 
x 
x 
x 
x 
x 
x 
 
Concomitant Medications (Infant) (daily) 
 
x 
x 
x 
x 
x 
x 
 
Study Drug Administration (daily) 
 
x 
x 
x 
x 
x 
 
 

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c. 
To be performed at per standard NICU protocols for assessment of ROP. 
d. Cranial ultrasound will be performed at between 5 and 7 days of age and at 28 (±3 days) of age for assessment of IVH; if neonate is discharged from the 
hospital prior to 28 days of age or the procedure is not clinically indicated, the cranial ultrasound may be deferred 
e. 
Assessments for BDP will be performed per NICU standard protocols by the attending physician and is defined as oxygen requirements at 36 weeks post 
conceptional age to keep oxygen saturation levels above 90%. 
f. 
Day 7 only. 
Protocol STP206-002 
Schedule of Events Post Dosing Period 
Procedure 
Week 1 
±2 days 
1 Month 
(Day 30 -35) 
3 Months 
(Day 85 – 99) 
6 Months 
(Day 181 – 195) 
Early Withdrawal| 
Prior to 6 Months 
Physical Examination  
x 
x 
x 
x 
x 
Vital Signs (Temp, BP, 
HR, RR)  
x 
x 
x 
x 
x 
Growth Assessment 
x 
x 
x 
x 
x 
Adverse Event 
Assessment 
x 
x 
x 
x 
x 
Concomitant 
Medications 
Evaluation (Infant) 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 

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APPENDIX B – DIAGNOSTIC CRITERIA FOR NEONATAL MORBIDITY  
Necrotizing Enterocolitis (NEC) 
Modified Bell’s Staging Criteria for NEC 
Stage 
Systemic 
Intestinal Signs 
Radiologic Signs 
IA - Suspected NEC 
Temperature instability, 
apnea, bradycardia, lethargy 
 
Elevated pre-gavage 
residuals, mild abdominal 
distension, emesis, guaiac. 
positive stool 
Normal or intestinal 
dilation, mild ileus 
 
IB - Suspected NEC 
 
Temperature instability, 
apnea, bradycardia, lethargy 
Bright red blood from rectum 
Normal or intestinal 
dilation, mild ileus 
 
IIA - Definite NEC 
Moderately ill 
Temperature instability, 
apnea, bradycardia, lethargy 
Bright red blood from 
rectum, PLUS absent bowel 
sounds, ± abdominal 
tenderness 
Intestinal dilation, ileus, 
pneumatosis intestinalis 
 
IIB - Definite NEC 
Temperature instability, 
apnea, bradycardia, lethargy 
PLUS mild metabolic 
acidosis, mild 
thrombocytopenia 
Bright red blood from 
rectum, absent bowel sounds, 
PLUS definite abdominal 
tenderness, ± abdominal 
cellulitis or right lower 
quadrant mass 
Intestinal dilation, ileus, 
pneumatosis intestinalis 
PLUS portal vein gas, 
± ascites 
 
IIIA - Advanced 
NEC, Severely ill 
Bowel intact 
 
Temperature instability, 
apnea, bradycardia, 
lethargy, mild metabolic 
acidosis, mild 
thrombocytopenia PLUS 
hypotension, bradycardia, 
severe apnea, combined 
respiratory and metabolic 
acidosis, disseminated 
intravascular coagulation, 
neutropenia 
Bright red blood from 
rectum, absent bowel sounds, 
definite abdominal 
tenderness, ± abdominal 
cellulitis or right lower 
quadrant mass PLUS signs of 
generalized peritonitis, 
marked 
tenderness, and distention of 
abdomen 
Intestinal dilation, ileus, 
pneumatosis intestinalis 
portal vein gas, definite 
ascites 
 
IIIB - Advanced 
NEC, Severely ill 
Bowel perforated 
 
Temperature instability, 
apnea, bradycardia, 
lethargy, mild metabolic 
acidosis, mild 
thrombocytopenia PLUS 
hypotension, bradycardia, 
severe apnea, combined 
respiratory and metabolic 
acidosis, disseminated 
intravascular coagulation, 
neutropenia 
Bright red blood from 
rectum, absent bowel sounds, 
definite abdominal 
tenderness, ± abdominal 
cellulitis or right lower 
quadrant mass PLUS signs of 
generalized peritonitis, 
marked 
tenderness, and distention of 
abdomen 
Intestinal dilation, ileus, 
pneumatosis intestinalis 
portal vein gas, definite 
ascites PLUS  
pneumoperitoneum 
 
From: Ped. Clinics of North America, February 1986, Walsh, M., Kliegman, R., Necrotizing enterocolitis: Treatment 
based staging criteria. 
 
 
 

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Retinopathy of Prematurity   
ROP is categorized in zones, with stages depicting the severity of the disease. The smaller and 
younger the infant at birth, the more likely the disease will involve the central zones with advanced 
stages.  
ROP is categorized by the lowest zone and the highest stage observed in each eye.  
Zones  
• 
Zone 1- is the most labile. The center of zone 1 is the optic nerve. It extends twice the distance 
from the optic nerve to the macula in a circle. Using a 28-diopter lens, if any portion of 
the optic nerve is in the same view as the ridge of ROP, that is considered zone 1.  
• 
Zone 2 - is a circle surrounding the zone 1 circle with the nasal ora serrata as its nasal border.  
• 
Zone 3 - is the crescent that the circle of zone 2 did not encompass temporally.  
Stages  
• 
Stage 0: This is the mildest form of ROP. It is immature retinal vasculature. No clear 
demarcation of vascularized and nonvascularized retina is present. Only a suggestion of 
the border is noted on examination.  
• 
Stage 1: A fine, thin demarcation line between the vascular and avascular region is present. This 
line has no height and no thickness.  
• 
Stage 2: A broad, thick ridge clearly separates the vascular from the avascular retina.  
• 
Stage 3: The extraretinal fibrovascular proliferation (neovascularization) may be present on the 
ridge, on the posterior surface of the ridge or anteriorly toward the vitreous cavity. The 
neovascularization gives the ridge a velvety appearance, a ragged border.  
• 
Stage 4: This stage is a subtotal retinal detachment beginning at the ridge. The retina is pulled 
anteriorly into the vitreous by the fibrovascular ridge.  
• 
Stage 5: This stage is a total retinal detachment in the shape of a funnel.  
 
 
 
 
 
 
 
 
 

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Bronchopulmonary Dysplasia 
• Clinical signs and symptoms consistent with neonatal lung disease 
• The subject meets specific NICHD diagnostic criteria specified in the table below. 
National Institute of Child Health and Human Development Criteria for  
Diagnosis of Bronchopulmonary Dysplasia (BPD)* 
< 32 Wk Gestational Age†  
Diagnosis†  
Need for < 30% O2 at 36 wk PMA or discharge, whichever comes 
first 
Mild to Moderate BPD 
Need for ≥ 30% O2, positive pressure or both at 36 wk PMA or 
discharge, whichever comes first 
Severe BPD 
*NOTE: These criteria are in addition to the baseline requirement of > 21% O2 for at least 
28 days. 
†Assessed at 36 wk postmenstrual age (PMA). 
Intraventricular Hemorrhage  
Hemorrhage noted on cranial ultrasonography: 
• 
Grade I - Hemorrhage of subependymal region and/or germinal matrix  
• 
Grade II -  Subependymal hemorrhage with extension into lateral ventricles without ventricular 
enlargement  
• 
Grade III - Subependymal hemorrhage with extension into lateral ventricles with ventricular 
enlargement  
• 
Grade IV -  Intraparenchymal hemorrhage 
 

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APPENDIX C – ANTIBIOTIC SUSCEPTIBILITY 
In the event of an infection due to 
 STP6 or 
 STP11, 
the minimum inhibitory concentrations (MICs) for 20 commonly used antibiotics are presented in 
the 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX E –  REVIEW OF INFECTIONS SUSPECTED TO INVOLVE 
STP206 ORGANISMS