Dietary Study of a Complex Oligosaccharide With and Without a Probiotic in Healthy Volunteers
Phase: NA
Conditions: Healthy Adult Subjects
Sponsor: Prolacta Bioscience

Official Title: Dietary Study of a Complex Oligosaccharide With and 
Without a Probiotic in Healthy Volunteers  
Identifiers: 
NCT04433208   Unique Protocol ID: 20-CT-001 
Document Date 03 May 2023 
 

 
 
CONFIDENTIAL 
This protocol and its contents are the property of and confidential to Prolacta Bioscience.  This information is provided for the 
exclusive use of the investigators participating in this study.  Any and all confidential information contained herein may not be 
disclosed to any other person or party without the prior written consent of Prolacta Bioscience. 
 
  
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TITLE PAGE 
CLINICAL STUDY PROTOCOL 
 
PROTOCOL TITLE: 
Dietary Study of Human Milk 
Oligosaccharides Concentrate  
PBCLN-005 with and without 
Bifidobacterium infantis in Healthy 
Adult Volunteers 
 
 
20-CT-001 – Revision 5 
 
SPONSOR: 
Prolacta Bioscience 
1800 Highland Ave. 
Duarte, CA 91010 
 
SPONSOR’S MEDICAL 
MONITOR: 
David J Rechtman, M.D. 
VP, Medical Affairs  
 
SPONSOR PROJECT 
MANAGER: 
Gregory McKenzie, Ph.D. 
VP, Product Innovation 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 2 of 30
 
SIGNATURE PAGE 
Author Signature: 
Date:  
David J Rechtman, M.D. 
VP, Medical Affairs  
 
 
This study protocol has been reviewed and approved by the undersigned persons.  It is confirmed 
that the information and guidance given in this protocol complies with scientific principles, the 
guidelines of Good Clinical Practices, the Declaration of Helsinki in the latest relevant version 
and the applicable legal and regulatory requirements.  
 
 
 Gloria Crockett 
Sr Director, Quality 
 
 
 
Date 
 Martin Lee, Ph.D. 
VP, Clinical Research & Development 
 
 
 
Date 
 Gregory McKenzie, Ph.D 
VP, Product Innovation 
 
 
 
Date 
 Adam Sun, Ph.D. 
VP, Research and Development 
 
 
Date 
 
Digitally signed by David J Rechtman 
M.D. 
Date: 2020.08.26 16:58:39 -07'00'
Gregory J McKenzie
Digitally signed by Gregory J 
McKenzie 
Date: 2020.08.26 20:02:47 -04'00'
Gloria M. Crockett
Digitally signed by Gloria M. 
Crockett 
Date: 2020.08.26 17:23:09 -07'00'
Martin L. Lee, 
PhD, CStat, CSci
Digitally signed by Martin L. Lee, 
PhD, CStat, CSci 
Date: 2020.08.26 17:40:05 -07'00'
Adam Sun
Digitally signed by Adam Sun 
Date: 2020.08.26 18:12:23 
-07'00'

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 3 of 30
 
INVESTIGATOR PROTOCOL AGREEMENT 
The signature below constitutes that I agree to the following: 
• I have reviewed the protocol and the attachments. 
• This trial will be conducted according to all stipulations of the protocol, including all 
statements regarding confidentiality, and according to local legal and regulatory requirements 
and applicable United States federal regulations, International Conference on Harmonization 
(ICH) guidelines, Health Insurance Portability and Accountability Act (HIPAA) guidelines. 
• I agree to periodic site monitoring of source documents by Prolacta Bioscience or designee 
and by appropriate regulatory authorities. 
• I agree to supply Prolacta Bioscience with any information regarding ownership interest and 
financial ties with the Sponsor for the purpose of complying with regulatory requirements. 
 
 
 
 
 
Investigator Name (Print) 
 
Investigator Signature 
 
Date 
 
 
 
 
 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
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TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................. 1 
SIGNATURE PAGE ................................................................................................................... 2 
INVESTIGATOR PROTOCOL AGREEMENT ........................................................................ 3 
TABLE OF CONTENTS ............................................................................................................ 4 
BACKGROUND AND RATIONALE ....................................................................................... 5 
BACKGROUND ......................................................................................................................... 5 
HYPOTHESIS ............................................................................................................................ 6 
METHODS.................................................................................................................................. 7 
TABLE 1 DOSING COHORTS ............................................................................................... 10 
SAMPLE SIZE .......................................................................................................................... 11 
STUDY DURATION ................................................................................................................ 11 
STUDY POPULATION ........................................................................................................... 11 
INCLUSION CRITERIA .......................................................................................................... 11 
EXCLUSION CRITERIA ......................................................................................................... 12 
STUDY PROCEDURE ............................................................................................................. 13 
STOOL SAMPLES ................................................................................................................... 14 
MICROBIOME SAMPLES ...................................................................................................... 14 
BLOOD SAMPLES .................................................................................................................. 15 
URINE SAMPLES .................................................................................................................... 15 
VITAL SIGNS .......................................................................................................................... 15 
SUBJECT STOOL COMPLIANCE ......................................................................................... 16 
SUBJECT IP COMPLIANCE .................................................................................................. 16 
STUDY ENDPOINTS .............................................................................................................. 17 
STATISTICAL EVALUATION............................................................................................... 18 
SCHEDULE OF EVENTS TABLES ....................................................................................... 19 
REFERENCES .......................................................................................................................... 30 
 
 
 

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BACKGROUND AND RATIONALE 
Dietary Study of Human Milk Oligosaccharide Concentrate PBCLN-005 with and without 
B. infantis in Healthy Adult Volunteers 
Background 
Human milk oligosaccharide (HMO) have recently become the objects of scientific inquiry. 
These complex sugars are extremely heat stable and are therefore found intact in donor milk and 
human milk-based products following pasteurization as well as in untreated mother’s own 
milk.i,ii,iii Approximately 200 different HMO structures have been identified, although any 
particular mother will only produce a subset of those. Studies have shown that HMOs can alter 
the gut microbiome by favoring the growth of certain organisms as well as, perhaps, by 
inhibiting others.4 It has also been demonstrated that HMOs can act as “decoy” receptors for a 
variety of pathogens and toxins.iv They have also been shown, in vitro, to directly interact with 
certain components of the adaptive immune system.4 
As a result of the aforementioned activities it is reasonable to expect that these molecules may be 
useful as therapeutic agents or medical foods. This is particularly the case in medical settings 
where the HMOs themselves or their metabolites may provide missing nutrients or other 
metabolic products for the dietary management of diseases where the microbiome plays a role, 
either in whole or in part. Examples might include conditions as disparate as inflammatory bowel 
disease and stem cell transplantation. 
We hypothesize that B. longum subspecies infantis (B. infantis) might be a particularly beneficial 
organism to expand in the microbiome when managing such diseases in combination with 
HMOs. In infants, co-administration of B. infantis with human milk (via breast feeding) results 
in expansion of B. infantis, reduction in other potentially deleterious species, notably members of 
the Family Enterobacteriaceae, and acidification of baby’s stool through the production of 
certain short chain fatty acids.7  These dietary effects are postulated to be due to metabolism of 
HMOs by B. infantis, as infants receiving human milk in the absence of B. infantis don’t show 
these effects.  Importantly, B. infantis is not observed as a constituent of the human adult gut 
microbiota so it may therefore be necessary to administer both HMOs and B. infantis to obtain 
the full beneficial impact of HMOs feeding in adults. 

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Prolacta Bioscience manufactures human milk-based products from donated breast milk. In the 
course of the manufacture of human milk-based human milk fortifier, skim breast milk is ultra-
filtered in order to concentrate proteins. Investigation of the permeate produced through this 
process demonstrated that human milk oligosaccharides were present in amounts comparable to 
those found in raw breast milk. Moreover, as the starting material consists of breast milk pooled 
from between 100 and 200 mothers, the full range of HMOs could be found. Subsequently, a 
method was developed to allow for the production of material with elevated concentrations of 
HMOs which contains little to no residual lactose through the introduction of lactase which is 
then removed.  
An unconcentrated, pasteurized form of HMO material containing a proportional amount of 
lactose has already been used in an NIH sponsored clinical trial in premature infants with no 
reported ill effects.v Prolacta Bioscience has also completed a healthy volunteer study using the 
same HMO material as in this trial (with no addition of  B. infantis) which showed good 
tolerability. No treatment emergent adverse effects were reported over the course of the trial.vi 
The B. infantis preparation being used in this trial is a dietary supplement commercially available 
in the United States and marketed for use in infants.  B. infantis is characterized as “generally 
regarded as safe” (GRAS).8 
Hypothesis 
The primary goal of this study is to evaluate the synergy of PBCLN-005 in varying doses with a 
fixed dose of B. infantis, compared with either component of the IP given alone.  Synergy is 
defined as the enhanced gastrointestinal colonization of B. infantis upon feeding with HMO 
feeding.  Secondary endpoints will measure changes in the gut microbiome, fecal metabolome 
and the subject’s immune status as measured by systemic markers. We hypothesize that the 
combination will result in greater proliferation of B. infantis than was seen with the HMO 
concentrate alone. 
Another objective is to understand the role of the low pH of the stomach in colonization of B. 
infantis. For most non-spore forming gut bacteria, the stomach is a barrier to colonization since 
acid exposure can reduce bacterial titer by 1,000- to 1,000,000-fold. While some subjects in the 
study will take a proton pump inhibitor (PPI; Zegerid), or a proton pump inhibitor (Zegerid) and 

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histamine H2-receptor antagonist (H2 blocker: Pepcid) to transiently reduce the production of 
gastric acid prior to B. infantis ingestion, some study groups will ingest B. infantis without PPI 
pretreatment. It was initially hypothesized that PPI might be necessary to observe B. infantis 
colonization distal to the acid milieu of the stomach. Preliminary data from the first group of 
subjects tested suggest that omeprazole may be inhibitory to B. infantis colonization and that 
colonization occurs in the absence of gastric acid suppression.  In vitro data suggest that the 
inhibitory effect is not seen with the histamine H2-receptor antagonist famotidine. Therefore, this 
has resulted in a change to this hypothesis. We now seek to determine if colonization occurs in 
the presence of an acidic milieu in the stomach, if the apparent inhibitory effect of PPI on 
colonization is real and if the prediction that the effect will not be seen with famotidine is correct 
because all target group subjects for future studies are on acid blockers.  
We also hypothesize that ingestion of PBCLN-005 along with the B. infantis will result in a more 
marked change in immune markers than was seen in the previous study in healthy adults. We 
will, therefore, evaluate changes in circulating cytokine and growth factor levels following the 
ingestion of the IP compared to baseline levels and between dose groups. 
Methods 
We propose to conduct an unblinded six cohort multi-dose trial using 10 subjects per cohort for a 
total of 60 healthy adult volunteers ages 18-44 in order to evaluate the effects of the use of HMO 
Concentrate (PBCLN-005) and B. infantis on the human microbiome.   
Six separate cohorts of both male and female study subjects will receive some form of the IP.  
All subjects in Cohort groups 1-4 and 6 will be followed from the day of the first dose of IP (day 
1) until 28 days (day 29) after the first dose.  Subjects in Cohort 1 will consume B infantis once 
per day for 7 days.  Subjects in Cohort 2-4 and Cohort 6 will consume the IP twice per day for 14 
consecutive days.  Cohorts 1-4 and Cohort 6 will be followed until the 28th day (day 29) 
following the first day of the feeding protocol (day 1).  
Subjects in Cohort 5 will receive two courses of IP; the first course will be accompanied with 
PPI. During the second course, some subjects will receive a H2 blocker, and some subjects will 
not.  Subjects will be followed from the day of the first dose of study drug (day 1) until 28 days 
after the first dose (day 29), and then from the first day of their second course (day 29) until the 

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28th day following the first dose of that course (day 57).  Subjects in that cohort will consume the 
HMO concentrate twice per day for 14 consecutive days during both courses of IP and will be 
followed until the 28th day following the first day of the second course of the feeding protocol for 
a total of 57 days.  
 
IP will be packaged so that consumption will be one container of each component per dose, to be 
mixed immediately prior to ingestion, except for Cohorts 1 and 2 where the IP will consist of 
only one container per dose.  
The PBCLN-005 will be presented in frozen liquid form while the B. infantis will be presented in 
a foil package as a lyophilized powder to be mixed with thawed PBCLN-005 or an appropriate 
alternative diluent prior to ingestion. 
Each bottle of HMO concentrate will be filled to deliver the required amount of HMO. The daily 
target doses of concentrated oligosaccharide to be evaluated in this study are 4.5g, 9g and 18g. 
The daily dose of B. infantis is ≥ 8X107 CFU in a foil pouch. The dosing cohort regime is 
outlined as follows. 
1. Study subjects randomized to Cohort 1 will consume by mouth B. infantis once per day 
for 7 consecutive days. Subjects will mix B. infantis in an aqueous diluent supplied by the 
pharmacy  
2. Study subjects randomized to Cohort 2 will consume by mouth the HMO investigational 
product (IP) twice per day for 14 consecutive days.   
3. Study subjects randomized to Cohort 3 will consume by mouth HMO investigational 
product (IP) twice per day for 14 consecutive days. B. infantis will be taken once per day 
for 7 consecutive days. The subject will mix HMO and B. infantis On days 8-14, only 
HMO product will be consumed (B. infantis will not be taken). 
4. Study subjects randomized to Cohort 4 will consume by mouth HMO investigational 
product (IP) twice per day for 14 consecutive days. B. infantis will be taken once per day 
for 7 consecutive days. The subject will mix HMO and B. infantis. On days 8-14, only 
HMO product will be consumed (B. infantis will not be taken). 
5. Study subjects randomized to Cohort 5 will undergo two consecutive dosing courses.  
During the first dosing course, they will consume by mouth HMO investigational product 

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(IP) twice per day for 14 consecutive days.  PPI and B. infantis will be taken once per day 
for 7 consecutive days. On dosing days 1-7 the first dose of HMO will be preceded by 
one hour and up to two hours by a single dose of PPI to protect the B. infantis from the 
acid milieu of the stomach.   The subject will mix HMO and B. infantis and ingest at least 
one hour after taking the PPI. On days 8-14, only HMO product will be consumed 
(neither the PPI nor B. infantis will be taken).  Cohort 5 will undergo a second dosing 
course from days 29-42. For all subjects, the HMO and B. infantis will be taken in the 
same manner as the first dosing course.  Note: Prior to Protocol Revision 4, two subjects 
have already been dosed in Cohort 5.  The first four of the remaining subjects yet to be 
enrolled in this cohort will take an H2 blocker in the same manner as the PPI in the first 
dosing course. The remaining four subjects enrolled into Cohort 5 will not take any PPI 
or H2 blocker during the second dosing course.   
6. Study subjects randomized to Cohort 6 will consume by mouth HMO investigational 
product (IP) twice per day for 14 consecutive days and B. infantis will be taken once per 
day for 7 consecutive days. On dosing days 1-7 the subject will mix one dose of HMO 
and B. infantis ingest. On days 8-14, only HMO product will be consumed (the B. infantis 
will not be taken).   
 
 

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Table 1 Dosing cohorts 
Cohort 
Target HMO 
Amount 
(days 1-14) 
PPI 
Cohort 5 Only 
(Course 1 = Days 1-7) 
H2 Blocker  
Cohort 5 Only 
(Course 2 = Days 29 – 35) 
B. infantis 
(days 1-7) 
1 
None 
No 
N/A 
Yes, one 
sachet 
2 
18g 
No 
N/A 
None 
3 
4.5g 
No 
N/A 
Yes, one 
sachet 
4 
9g 
No 
N/A 
Yes, one 
sachet 
5A 
18g 
Yes 
  Yes (4 subjects) 
 No (4 subjects) 
Yes, one 
sachet 
6 
18g 
No 
N/A 
Yes, one 
sachet 
A This group will undergo two dosing courses. One from day 1-14 and one from day 29-42.  Four of the 
subjects in the second course will be assigned a H2 blocker and four of the subjects will not take any PPI 
or H2 blocker.  
NOTE: Prior to Protocol Revision 4, two subjects were enrolled in Cohort 5 based on the original dosing 
scheme.  Thus, two subjects have already been dosed in Cohort 5.  The first four of the remaining subjects 
yet to be dosed in the Cohort 5 second dosing course will take a H2 blocker in the same manner as the 
PPI in the first dosing course. The remaining four subjects enrolled into Cohort 5 will not take any PPI or 
H2 blocker during the second dosing course. 
As the maximum quantity of human milk oligosaccharides in this study has previously been 
given to healthy adult volunteers with good tolerance and no treatment emergent adverse events6, 
this study will not be conducted in the manner of a dose escalation safety study. That is, the 
randomization scheme will allow for the assignment of any given study subject to any of the six 
cohorts rather than to fill the cohorts sequentially. 
Samples of blood, urine and stool from all subjects will be taken at screening (day 0) to 
determine subject eligibility and to establish baseline values. Urine will only be required at 
screening.  Stool samples will also be required on days 1, 5, 8, 15, 22 and 29, where day 1 is the 
first day of the feeding protocol. Blood samples will also be drawn on days 1, 8, 15, and 29.  For 
dose group 5 ONLY, stool samples will also be required on days 33, 36, 43, 50 and 57 and blood 
samples on days 36, 43 and 57.  Details regarding type of stool sample and its processing is 
described in the accompanying Laboratory Manual. 
The summary of all study events is presented in Table 2 at the end of this protocol. 

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Sample Size 
Six groups of 10 subjects will be included in this study for a total sample size of 60. The sample 
size was not determined statistically, but rather represents a typical number for an exploratory 
study of healthy volunteers. 
Study Duration 
Six separate cohorts of both male and female study subjects will receive some form of the IP.  
All subjects in Cohorts 1-4 and 6 will be followed from the day of the first dose of IP (day 1) 
until 28 days (day 29) after the first dose.  Subjects in Cohort 1 will consume B infantis once per 
day for 7 days.  Subjects in Cohort 2-4 and Cohort 6 will consume the IP twice per day for 14 
consecutive days.  Cohorts 1-4 and Cohort 6 will be followed until the 28th day (day 29) 
following the first day of the feeding protocol (day 1).  
Subjects in Cohort 5 will receive two courses of IP. They will be followed from the day of the 
first dose of study drug (day 1) until 28 days after the first dose (day 29), and then from the first 
day of their second course (day 29) until the 28th day following the first dose of that course (day 
57).  Subjects in that cohort will consume the HMO concentrate twice per day for 14 consecutive 
days  during both courses of IP and will be followed until the 28th day following the first day of 
the second course of the feeding protocol for a total of 57 days.  
Study Population 
Each subject must meet all of the indicated inclusion criteria and none of the exclusion criteria 
noted below.  
Inclusion Criteria 
• Healthy adults between the ages of 18-44 years (subjects must be 18-44 at the time of 
consent) 
• Willingness to complete study specific questionnaires 
• Willingness to complete journal to record IP dosing times 
• Willingness to complete all study procedures and clinic visits, and provide required 
samples 
• Able to provide stool samples on specific study days 

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• Willingness to collect and process stool samples at home and transport stool samples 
to clinic 
• Bristol Stool Score of 1 through 5 at time of screening and on day 1, subjects must 
verbally confirm that they did not have stool conforming to Bristol Stool Score 6 or 7 
during the 7 days prior to dosing. 
• Able to store up to 9 days of IP in refrigerator  
• Sexually active females of child-bearing potential must agree to use highly effective 
methods of contraception during heterosexual intercourse throughout the study period 
and for three days following discontinuation of IP, whichever comes later.   Examples 
of highly effective methods include the use of two forms of contraception with one 
being an effective barrier method (e.g., a condom and spermicide used together), or 
have a vasectomised partner. Abstinence is acceptable as a life-style choice. Female 
subjects who utilize hormonal contraceptives as one of their birth control methods 
must have used the same method for at least 3 months before study dosing 
• Provides informed consent  
Exclusion Criteria 
• Women who are pregnant or breastfeeding, or intend to become pregnant during the 
course of this study 
• Subjects with allergy to, or other reason for contraindication of the PPIs or H2 
blocker* chosen for this study.   
o *The H2 blocker allergy or contraindication exclusion only applies to Subjects 
enrolled in Cohort 5 that are scheduled to receive an H2 blocker.  Cohort 5 
Subjects with an H2 blocker allergy or contraindication may be assigned to 
the second dosing course without an acid blocker. 
• Subjects with history of lactose intolerance 
• Subjects who are on a PPI regimen 
• Subject who has taken a probiotic during the previous 30 days prior to first dose, or 
intends to take a probiotic during the study 
• Subject who has taken antibiotics within 120 days prior to first dose 

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• Alcohol or drug abuse during the last 12 months, including passing a screen for drugs 
of abuse at screening  
• Unstable medical condition, in the opinion of the investigator 
• Clinically significant abnormal laboratory test results at screening 
• Subjects who are unable or unwilling to provide stool samples on a regular basis 
• Participation in a clinical research trial within 30 days prior to screening 
• Unable to give informed consent 
• Any condition which may preclude subject’s ability to comply with and complete the 
study or may pose a risk to the health of the subject. 
• Known carriers of B. infantis prior to study start, as determined by qPCR of stool 
Patients with pending screening test results will be allowed to proceed. 
• Bristol Stool Score of 6 or 7 at time of screening  and on day 1, subject reported 
Bristol Stool Scores of 6 or 7 for any of the 7 days prior to dosing.  If there is 
difficulty distinguishing between a Bristol Stool score of 5 or 6, a Bristol Stool Score 
of 6 will only be assigned if the subject has a GI clinical indication.  
Study Procedure 
Screening Visit (day 0, may occur up to and including 90 days prior to the subject’s dose.  After 
informed consent is obtained and subject eligibility is assessed, vital signs, samples of blood, 
stool, and urine will be obtained from subjects at screening visit (day 0).  Prior to dosing on day 
1, subject eligibility will be reassessed, vital signs, samples of blood, and stool will be obtained 
from subjects.  On days 1-14, subjects in Cohorts 2-6 will consume the HMO concentrate twice 
daily. On days 1-7, Cohort 5 will ingest a PPI one hour prior to ingesting the HMO concentrate 
or an aqueous diluent (Cohort 1 only). Additionally, on days 1-7, Cohorts 1 and 3-6, subjects will 
ingest B. infantis admixed with the HMO solution or an aqueous diluent (Cohort 1 only).  For 
Cohort 5 only, the same pattern will be repeated on study days 29-42. The first four of the 
subjects yet to be enrolled in this cohort will take a H2 blocker in the same manner as the PPI in 
the first dosing course. The remaining four subjects enrolled into Cohort 5 will not take any PPI 
or H2 blocker during the second dosing course.   

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Samples of blood, urine and stool from all subjects will be taken at screening. Stool samples will 
also be required on days 1, 5, 8, 15, 22 and 29. Blood samples will also be drawn on days 1, 8, 
15, and 29. For dose group 5 ONLY, additional stool samples will also be required on days 33, 
36, 43, 50 and 57 and blood samples on days 36, 43 and 57. 
Stool Samples 
Stool samples collected at screening (day 0) will be analyzed by qPCR to determine if the subject 
is a carrier of B. infantis.  Screening (day 0) stool samples collected for metabolomic and 
metagenomic testing will not be used to determine patient eligibility.  
 
Stool samples will be tested for microbiome, metabolomics and metagenomics.  At-home stool 
samples will be collected on days 5, 22, 33 and 50 (+1 day).  Day 33 and 50 applies to dose 
group 5 ONLY. The At-home stool samples will be collected by the subject into the Omnigene-
Gut OMR-200 collection tube (DNA Genotek; Ottawa, Canada). On days 1, 8, 15, 29 (+2 days, 
excluding day 1), and days 36, 43, and 57 (+2 days) for dose group 5 only, subjects will deposit 
their stool in a provided collection kit and bring the entire sample to the clinic for processing by 
the site.  Alternatively, on these days the subjects may opt to provide the specimen during the 
course of visit to the study center. Collection and stool processing procedures are described in 
the accompanying Laboratory Manual. 
 
Microbiome Samples 
Stool samples for microbiome analysis will be prepared for DNA extraction.  After DNA 
extraction, a sample will be analyzed using species- and strain-specific quantitative PCR analysis 
to evaluate B. infantis colonization both during and after HMO ingestion.  Selected samples may 
also be analyzed by next generation DNA sequencing to determine the taxonomic composition, 
alpha- and beta-diversity and change of each subject’s microbiome during the study.  Methods 
may include 16S and/or whole metagenomic shotgun sequencing and culture-specific methods as 
deemed appropriate by the Sponsor. 
Aliquots of stool from Days 1, 8, 15, 29 (+2 days, excluding day 1) and days 36, 43, 57 (+2 
days) for dose group 5 only, will be aliquoted and frozen at -70 deg C or colder immediately 

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after collection. These samples will be provided to contractor(s) with metabolomic capabilities to 
measure production of short chain fatty acids, levels of HMO, and other microbial metabolites as 
deemed appropriate by the Sponsor.    
  
Blood Samples 
Blood samples collected at screening (day 0) will be used to determine subject eligibility and 
baseline results.  Blood samples will be collected and tested for the purpose of safety monitoring 
on days 1, 15, 29, (+2 days, excluding day 1) and days 43, and 57 (+2 day) for Cohort 5 ONLY.  
Specifically, the following tests will be performed: CBC with differential and platelets; alkaline 
phosphatase, ALT, AST, LDH, total and conjugated bilirubin, albumin, and total protein for liver 
function; electrolytes Na, K, Cl, HCO3, and glucose; total calcium, magnesium, and phosphate; 
creatinine and BUN for renal function. Blood will also be taken at screening to test for markers 
of immunological activity, including but not limited to, TGFβ.  Immunology samples taken at 
screening will not be used for subject eligibility. Additional immunological blood samples will 
be drawn on day 8 (+2 days), and on day 36 (+2 days) for Cohort 5 ONLY.    
 
All blood testing for safety and immunological testing will be performed at a central clinical 
laboratory. 
Urine Samples 
Urine samples collected at screening (day 0) will be used to screen for drugs of abuse.  Females 
of child-bearing potential will also provide urine for screening pregnancy tests at screening (day 
0).  If child-bearing status is unknown, a urine pregnancy test should be performed at screening. 
 
Vital Signs 
Vitals signs, including temperature, blood pressure (BP), pulse, and respiration rate (RR), will be 
taken at screening (day 0), day 1 and all follow up clinic visits days 8, 15, 29, 36, 43 and 57.  
Days 36, 43 and 57, only apply to subjects in Cohort 5.  Subjects should rest for at least 10 mins 
prior to taking vitals. Vitals should be taking prior to any blood draws and in a sitting or supine 

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position.  Height, weight and body mass index (BMI) will be taken only at the screening visit 
(day 0). 
Subject Stool compliance 
Subjects will be considered evaluable if each subject provides 80% of samples through day 21.  
Subjects who do not meet this criterion will be replaced.  Subjects that are identified as B. 
infantis carriers at the time of screening may be replaced depending when stool test is resulted. 
Subject IP compliance 
Subject compliance will be evaluated in 2-ways: 
• Subjects will return all IP (used and unused containers for PBLCN-005 and B. infantis) to 
the clinical site on days 8 and 15 for reconciliation by the Pharmacy. 
• Subjects will record the date and times that the subject ingested IP in a take home journal.  
• The study site will use a defined mechanism (daily phone call and/or text messaging and/ 
daily email) to remind subject regarding daily dose and to gain confirmation that dosing 
has been completed.  Any phone, text and/or email interactions will be documented as 
part of the study records. 
• In addition, the metabolomic measurement of HMO and the quantitative measurement of 
B infantis will provide additional evidence of subject compliance (albeit after the fact). 
• Subjects who miss a dose of their PPI or H2 blocker (Cohort 5 only) or B. infantis or both 
(Cohort 5 only), will make up the missed dosed by adding one additional dosing day of 
PPI, H2 blocker, or B infantis or both to their dosing regimen.  No more than 2 
consecutive missed doses or 3 missed are allowed over the study.  Subjects who do not 
meet these criteria may be replaced. 
• Subjects who miss a dose of PBCLN-005, will make up the missed dosed by adding one 
additional dose of PBCLN-005 to their dosing regimen.  No more than 2 consecutive 
missed doses of PBCLN-005, or 3 missed doses of PBCLN-005 are allowed total over 
study.  For Cohort 5, this applies to each dosing period.  Subjects who do not meet this 
criterion may be replaced. 

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Study endpoints 
A data collection spreadsheet will be provided in order to capture the relevant information that 
will be obtained by the clinical site indicated below.  For primary endpoint and microbiome 
/metabolomic data, the Sponsor will be responsible for capturing data and incorporating into an 
appropriate database. 
a) Primary Endpoint 
• The primary endpoint will be changes in the level of B. infantis from baseline evaluated 
by quantitative PCR using primers for species and strain.  Quantitation limits will be 
demonstrated by qualification assays demonstrating the lower limit of detection, in order 
to establish minimum log-fold change in B. infantis, as it is expected that adult subjects 
will not harbor B. infantis in baseline samples. 
b) Secondary Endpoints 
• Changes in stool microbiota will be measured as well as dynamic changes in the gut 
community structure. These changes will be evaluated by next generation sequencing 
using proportions of key bacterial operational taxonomy units (OTUs), relative 
abundance of various taxa, diversity (alpha and beta) and stability of communities and 
functional metabolomic changes. 
• Changes in viability of proteobacteria and Enterococcus will be determined by plating on 
selective media.  These measurements will predictive for success in suppressing 
pathogenic bacterial relatives in future trials. 
• Blood parameters, such as cytokine levels at study days -1, 8, 15 and 2 except for Cohort 
5 who will also be evaluated on days 36, 43 and 57. 
• Determination of the need for protection of B. infantis from stomach acid in order for 
engraftment of the organism into the gut microbiome to occur. 
c) Adverse events will be summarized by severity and relationship to study product. All adverse 
events will be reported on the study case report form designated for this purpose. Any serious 
and unexpected adverse event determined by the investigator to be definitely or highly likely 
causally related with the consumption of IP should be reported immediately (but no later than 
within 24 hours) to the Sponsor’s Medical Monitor. 
d) Baseline measures as of study entry 
e) IP Feeding Protocol 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 18 of 30
 
f) The dose level of PBCLN-005 consumed will be recorded as well as consumption of B 
infantis. 
g) Demographics; age, gender, ethnicity and race 
h) Stool changes in subject’s stool per Bristol Stool Score  
i) IP taste/ flavor on dosing days using a visual acuity scale 
Statistical evaluation 
Since this is an initial study of the use of PBCLN-005 in combination with B infantis, it is, by 
definition, hypothesis-generating. Therefore, all statistical analyses will be descriptive. The 
various indices reflecting the microbiome will be summarized with appropriate descriptive 
statistics at each day of collection and compared qualitatively across time and by dose.  Other 
quantitative outcome data collected will be summarized by means/medians and standard 
deviations/inter-quartile ranges. Graphics such as box plots also will be presented. Safety data 
(tolerability and adverse events) will be presented in tables with proportions (per subject) by 
dose and overall.

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 19 of 30
 
Schedule of Events Tables 
Schedule of Events Table 
Cohort 1 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 1 (Day 0 through Day 29) 
Events 
Cohort 1  
Screening 
Cohort 1  
Dosing Days 
Cohort 1  
Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to 
D1)   
Clinic visit 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Final Visit  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 X 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Review IE Criteria 
X 
X  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Exam 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X  
Demographics (age, 
gender, ethnicity and 
race 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital Signs (Temp, 
BP, pulse, RR) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Height, weight and 
BMI 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prior & Con Meds 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
AEs 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 20 of 30
 
Cohort 1 (Cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 1 (Day 0 through Day 29) 
Events 
Cohort 1 
Screening 
Cohort 1  
Dosing Days 
Cohort 1 
Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to 
D1)   
Randomization 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Dispense IP:   B. infantis 
(≥8x107 cfu/d) and aqueous 
dilute 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dosing: B. infantis (≥8x107 
cfu/d)  
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
Assess IP and Stool 
compliance   
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
 X 
Stool Questionnaires 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Daily Dosing and Flavor 
Questionnaire  
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
Patient Phone Calls 
  
  
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 21 of 30
 
Cohort 1 (cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 1 (Day 0 through Day 29) 
Events 
Cohort 1  
Screening 
Cohort 1  
Dosing Days 
Cohort 1 
Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to 
D1)   
Urine Drug Screen 
Test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy Test 
(Females of child-
bearing potential) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology &  
Chemistry testing 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
X 
 Immunology testing  
(Screening samples 
will not be evaluated 
for eligibility) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool 
(metagenomics) 
(Screening samples 
will not be evaluated 
for eligibility) 
X 
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Stool (metabolomics) 
(Screening samples 
will not be evaluated 
for eligibility) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool (microbiology) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Fecal pH (using 
nitrazine paper) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 22 of 30
 
Schedule of Events Table 
Cohorts 2, 3, 4, and 6 
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 2, 3, 4, & 6 (Day 0 through Day 29) 
Events 
Cohorts 2, 3, 
4, & 6 
Screening 
Cohorts 2, 3, 4, & 6  
Dosing Days 
Cohorts 2, 3, 4, 
& 6 Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to D1)   
Clinic visit 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Final Visit  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 X 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Review IE Criteria 
X 
 X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Exam 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X  
Demographics (age, 
gender, ethnicity and 
race 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital Signs (Temp, 
BP, pulse, RR) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Height, weight and 
BMI 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prior & Con Meds 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
AEs 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 23 of 30
 
Cohorts 2, 3, 4, and 6 (cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 2, 3, 4 & 6 (Day 0 through Day 29) 
Events 
Cohorts 2, 
3, 4, & 6 
Screening 
Cohorts 2, 3, 4, & 6  
Dosing Days 
Cohorts 2, 3, 
4, & 6  
Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to 
D1)   
Randomization 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Dispense IP:,  B. infantis (≥8x107 
cfu/d) (except Cohort 2) 
(Note: On D1 dispense 9-day 
supply of PBCLN-005.  On D8 
dispense 5-day supply of  PBCLN-
005)  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
Dosing: B. infantis (≥8x107 cfu/d) 
(All Cohorts except Cohort 2) 
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
Dosing: PBCLN-005 1 bottle po 
bid (Target 4.5g, 9g or 18g)  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
Assess IP and Stool compliance  
 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 Stool Questionnaire  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Daily Dosing and Flavor 
Questionnaire  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
Patient Phone Calls  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 24 of 30
 
Cohorts 2, 3, 4 & 6 (cont.)  
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 2, 3, 4, & 6  (Day 0 through Day 29) 
Events 
Cohorts 2, 
3, 4, & 6 
Screening 
Cohorts 2, 3, 4, & 6  
Dosing Days 
Cohorts 2, 3, 4, 
& 6 Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to D1)   
Urine Drug Screen Test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy Test 
(Females of child-
bearing potential) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology &  
Chemistry testing 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
X 
Immunology testing  
(Screening samples will 
not be evaluated for 
eligibility)  
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool (metagenomics) 
(Screening samples will 
not be evaluated for 
eligibility) 
X 
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Stool (metabolomics) 
(Screening samples will 
not be evaluated for 
eligibility) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool (microbiology) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Fecal pH (using nitrazine 
paper) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 25 of 30
 
Schedule of Events Table 
Cohort 5 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 5 (Day 0 through Day 22) 
Events 
Cohort 5 
Screening 
Cohort 5  
1st Dosing Course 
Cohort 5   1st 
Washout  
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
(≤ 90 days 
prior to D1)   
Clinic visit 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Informed consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Review IE Criteria 
X 
 X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Exam 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Demographics (age, 
gender, ethnicity and 
race 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital Signs (Temp, 
BP, pulse, RR) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Height, weight and 
BMI 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prior & Con Meds 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
AEs 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 26 of 30
 
Cohort 5 (Cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 5 (Day 0 through Day 22) 
Events 
Cohort 5 
Screening 
Cohort 5  
1st Dosing Course 
Cohort 5    
1st Washout 
period 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
(≤ 90 days 
prior to 
D1)   
Randomization 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Dispense IP: PPI, B. infantis 
(≥8x107 cfu/d) (Note: On D1 
dispense 9-day supply of PBCLN-
005.  On D8 dispense 5-day supply 
of  PBCLN-005)  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
Dosing: PPI  
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
Dosing: B. infantis (≥8x107 cfu/d)  
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
Dosing: PBCLN-005 1 bottle po 
bid (18g)  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
Assess IP and Stool compliance  
 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Stool Questionnaire  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Daily Dosing and Flavor 
Questionnaire  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
Patient Phone Calls  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 27 of 30
 
Cohort 5 (Cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 5  (Day 0 through Day 22) 
Events 
Cohort 5 
Screening 
Cohort 5  
1st  Dosing Course 
Cohort 5     
1st  Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
(≤ 90 days 
prior to D1)   
Urine Drug Screen Test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy Test 
(Females of child-
bearing potential) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology &  
Chemistry testing 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
Immunology testing  
(Screening samples will 
not be evaluated for 
eligibility)  
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Stool (metagenomics) 
(Screening samples will 
not be evaluated for 
eligibility) 
X 
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
X 
X 
Stool (metabolomics)    
(Screening samples will 
not be evaluated for 
eligibility) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Stool (microbiology) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Fecal pH (using 
nitrazine paper) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 28 of 30
 
Cohort 5 (Cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 5 Only (Day 29 through Day 57) 
Events 
Cohort 5  
2nd Dosing Course 
Cohort 5  
2nd Washout Period 
D29 
D30 
D31 
D32 
D33 
(+1D) 
D34 
D35 
D36 
(+2D) 
D37 
D38 
D39 
D40 
D41 
D42 
D43 
(+2D) 
D50      
(+2D) 
D57 
(+2D) 
Clinic visit 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Review IE Criteria1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Final Visit 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 X 
Physical Exam 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Vital Signs (Temp, 
BP, pulse, RR) 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Prior & Con Meds 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
AEs 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Dispense IP: H2 
blocker (if 
applicable) 2, B. 
infantis (≥8x107 
cfu/d) 
(Note: On D29 
dispense 9-day 
supply of PBCLN-
005.   
On D36 dispense  
5-day supply of  
PBCLN-005) 
X2 
  
  
  
  
  
  
X2 
  
  
  
  
  
  
  
  
  
Dosing: H2 blocker2 
X2 
X2 
X2 
X2 
X2 
X2 
X2 
  
  
  
  
  
  
  
  
  
  
Dosing: B. infantis 
(≥8x107 cfu/d)  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
Dosing: PBCLN-
005 (Target 18g)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
1Subjects will be assessed for an H2 blocker allergy or contraindication prior to dosing in the second dosing course with the H2 blocker  
2The first four of the subjects yet to be enrolled in this cohort will take a H2 blocker in the same manner as the PPI in the first dosing course. The remaining four subjects enrolled 
into Cohort 5 will not take any PPI or H2 blocker during the second dosing course.   
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 29 of 30
 
Cohort 5 (cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 5 (Day 29 through Day 57) 
Events 
Cohort 5  
2nd Dosing Days 
Cohort 5 
Only 
Washout 
D29 
D30 
D31 
D32 
D33 
(+1D) 
D34 
D35 
D36 
(+2D) 
D37 
D38 
D39 
D40 
D41 
D42 
D43 
(+2D) 
D50 
(+2D) 
D57 
(+2D) 
Assess IP and 
Stool compliance   
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool  
Questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Daily Dosing and 
Flavor 
Questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
Patient Phone 
Calls 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
Hematology &  
Chemistry testing 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
X 
Immunology 
testing  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool 
(metagenomics) 
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Stool 
(metabolomics) 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool 
(microbiology) 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Fecal pH (using 
nitrazine paper) 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 
 
 

Protocol Number: 20-CT-001 
Rev. 5 
CONFIDENTIAL 
Page 30 of 30
 
References 
i Barile D, Lebrilla DBC, German B, Rechtman DJ, and Lee ML. Oligosaccharide prebiotics  present in a 
breast milk based human milk fortifier. Presented at Hot Topics in Neonatology. Washington DC  
December 2008 
ii Barile D, German B, Lee ML, and Rechtman DJ. Potential Novel Source for Human Oligosaccharides. Presented 
at American Academy of Pediatrics National Conference and Exhibit, Washington DC 2009. 
 
iii Ninonuevo M., Park Y., YIN H., Zhang J., Ward R.E., Clowers B.H., German J.B., Freeman S.L., 
Killeen K., Grimm R., and Lebrilla C.B.(2006) A strategy to annotate the human milk glycome. J.Agric. 
Food Chem. 54: 7471-7480] 
 
iv Smilowitz JT, Lebrilla CB, Mills DA, German JB, and Freeman SL. Breast Milk Oligosaccharides: 
Structure-Function Relationships in the Neonate. Annu Rev Nutr. 2014 ; 34: 143–169. 
 
v Underwood MA, Kalanetra KM, Bokulich NA et al. Prebiotic oligosaccharides in premature infants. 
JPGN 2014;58: 352–360 
 
vi Prolacta Bioscience unpublished data on file 
 
7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450358/ 
 
8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114170/ 
 
 
 

Statistical Analysis Plan 
 
 
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Page 1 of 26 
STATISTICAL ANALYSIS PLAN 
 
Protocol: 20-CT-001 
Dietary Study of Human Milk Oligosaccharides Concentrate PBCLN-005 with and without 
Bifidobacterium infantis in Healthy Adult Volunteers 
 
SAP Version: 1.0 
Date of Final Change: 4/18/2023 
Published Date:  4/18/2023 
 
 
This document contains confidential information and is the proprietary property of Prolacta Bioscience. This 
document may not be copied or made available for review by an unauthorized person or firm without the prior 
written authorization of Prolacta Bioscience. 
 
 
 
 
 
 
 
 
Date 
 
Prepared by:  Sheryl O’Rourke, MS, Consultant 
 
 
 
 
Date 
 
Approved by: Martin Lee, PhD, CStat, CSci.. Vice-
President Clinical Research and Development 
 
 
 
 
 
Date 
 
Approved by: David Rechtman, MD. Vice-President, 
Medical Affairs 
 
 
 
 
 
Martin L. Lee, 
PhD, CStat, CSci, 
FIBMS
Digitally signed by Martin L. 
Lee, PhD, CStat, CSci, FIBMS 
Date: 2023.04.19 11:06:01 
-07'00'
Digitally signed by David J 
Rechtman M.D. 
Date: 2023.04.20 13:48:19 -07'00'
Sheryl 
O'Rourke, MS
Digitally signed by 
Sheryl O'Rourke, MS 
Date: 2023.04.21 
09:34:48 -07'00'

Statistical Analysis Plan 
 
 
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Revision History 
 
Version # 
Date 
Effective 
Page/Section/ 
Paragraph 
Change From: 
Change To: 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
TABLE OF CONTENTS ..............................................................................................................3 
1 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .......................5 
2 
SCOPE OF THE STATISTICAL ANALYSIS PLAN ..........................................6 
3 
INTRODUCTION ....................................................................................................6 
3.1 
Preface ........................................................................................................................6 
3.1 
The Purpose of the analyses........................................................................................7 
3.2 
Study Endpoints ..........................................................................................................8 
3.2.1 
Primary........................................................................................................................8 
3.2.2 
Secondary....................................................................................................................8 
3.2.3 
Safety ..........................................................................................................................8 
4 
STUDY METHODS .................................................................................................9 
4.1 
Study DESIGN ...........................................................................................................9 
4.2 
Inclusion/Exclusion criteria and the general patient population ...............................10 
4.2.1 
Inclusion Criteria ......................................................................................................10 
4.2.2 
Exclusion Criteria .....................................................................................................10 
4.3 
Randomization and blinding .....................................................................................11 
4.4 
schedule of Events ....................................................................................................12 
4.5 
sample size ................................................................................................................21 
4.6 
timing of analyses .....................................................................................................21 
4.7 
Analysis Populations.................................................................................................21 
4.8 
Missing Data .............................................................................................................21 
4.9 
Interim analyses and Data monitoring ......................................................................21 
5 
SUMMARY OF STUDY DATA ............................................................................21 
5.1 
Subject Disposition ...................................................................................................21 
5.2 
Protocol Deviations...................................................................................................22 
5.3 
Demographic and Baseline variables ........................................................................22 
6 
PRIMARY ENDPOINT ANALYSES ...................................................................23 
7 
SECONDARY ENDPOINT ANALYSES .............................................................23 
7.1 
Changes in stool microbiota .....................................................................................23 

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7.1.1 
Fecal Microbial Diversity .........................................................................................23 
7.2 
Changes in viability of proteobacteria and Enterococcus .........................................23 
7.3 
Changes in Blood parameters ...................................................................................23 
7.4 
Evaluation of the use of proton pump inhibitors for protection of B. infantis .........23 
8 
SAFETY EVALUATION.......................................................................................23 
8.1 
Adverse Events .........................................................................................................24 
8.2 
Clinical laboratory evaluations .................................................................................24 
8.3 
Vital Signs.................................................................................................................24 
9 
TECHNICAL DETAILS ........................................................................................24 
10 
CHANGES IN CONDUCT OF STUDY OR TO PLANNED ANALYSES 
FROM PROTOCOL ..............................................................................................25 
11 
REFERENCES........................................................................................................25 
12                 LISTING OF TABLES, LISTINGS, AND FIGURES TABLES ........25 
 
 
 
 
 
 

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1 
LIST OF ABBREVIATIONS AND DEFINITIONS 
OF TERMS  
Abbreviation 
Definition 
AE 
Adverse event 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase 
BUN 
Blood urea nitrogen 
BMI 
Body-mass index 
CRF 
Case report form 
CRO 
Clinical research organization 
DSMB 
Data and safety monitoring board 
EIA 
Enzyme immunoassay 
FDA 
Food and Drug Administration 
GRAS 
Generally regarded as safe 
GDH 
Glutamate dehydrogenase 
GCP 
Good clinical practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HMO 
Human milk oligosaccharide 
ID 
Identification number 
IEC 
Independent ethics committee 
IP 
Investigational product 
ISDA 
Infectious Disease Society of America 
IRB 
Institutional review board 
ICH 
International Conference on Harmonization 
NDA 
Investigational New Drug 
LDH 
Lactate dehydrogenase 
LNnT 
Lacto-N-neotetraose 
NGS 
Next-generation sequencing 
NAAT 
Nucleic acid amplification tests 
OTU 
Operational taxonomic unit 
OTC 
Over the counter 

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Abbreviation 
Definition 
PO 
Per os 
RTF 
Ready-to-feed 
SAE 
Serious adverse event 
SHEA 
Society of Hospital Epidemiologists of America 
VRE 
Vancomycin-resistant Enterococci 
2 
 SCOPE OF THE STATISTICAL ANALYSIS 
PLAN 
This version of the Statistical Analysis Plan (SAP) will focus on the safety analyses described in 
the protocol. These analyses will be included in an initial abbreviated safety report.  The details 
of the analysis of primary and secondary endpoints are included here but will be expanded upon 
in an amended SAP for the full clinical study report. 
3 
INTRODUCTION 
3.1 
PREFACE 
Human milk oligosaccharide (HMO) have recently become the objects of scientific inquiry. These 
complex sugars are extremely heat stable and are therefore found intact in donor milk and human 
milk-based products following pasteurization as well as in untreated mother’s own milk.1,2,4 
Approximately 200 different HMO structures have been identified, although any particular mother 
will only produce a subset of those. Studies have shown that HMOs can alter the gut microbiome by 
favoring the growth of certain organisms as well as, perhaps, by inhibiting others.4 It has also been 
demonstrated that HMOs can act as “decoy” receptors for a variety of pathogens and toxins.4 They 
have also been shown, in vitro, to directly interact with certain components of the adaptive immune 
system.4  
As a result of the aforementioned activities, it is reasonable to expect that these molecules may be 
useful as therapeutic agents or medical foods. This is particularly the case in medical settings where 
the HMOs themselves or their metabolites may provide missing nutrients or other metabolic products 
for the dietary management of diseases where the microbiome plays a role, either in whole or in part. 
Examples might include conditions as disparate as inflammatory bowel disease and stem cell 
transplantation.  
We hypothesize that B. longum subspecies infantis (B. infantis) might be a particularly beneficial 
organism to expand in the microbiome when managing such diseases in combination with HMOs. In 
infants, co-administration of B. infantis with human milk (via breast feeding) results in expansion of 
B. infantis, reduction in other potentially deleterious species, notably members of the Family 

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Enterobacteriaceae, and acidification of baby’s stool through the production of certain short chain 
fatty acids.7 These dietary effects are postulated to be due to metabolism of HMOs by B. infantis, as 
infants receiving human milk in the absence of B. infantis don’t show these effects. Importantly, B. 
infantis is not observed as a constituent of the human adult gut microbiota so it may therefore be 
necessary to administer both HMOs and B. infantis to obtain the full beneficial impact of HMOs 
feeding in adults. 
Prolacta Bioscience manufactures human milk-based products from donated breast milk. In the 
course of the manufacture of human milk-based human milk fortifier, skim breast milk is ultra-
filtered in order to concentrate proteins. Investigation of the permeate produced through this process 
demonstrated that human milk oligosaccharides were present in amounts comparable to those found 
in raw breast milk. Moreover, as the starting material consists of breast milk pooled from between 
100 and 200 mothers, the full range of HMOs could be found. Subsequently, a method was 
developed to allow for the production of material with elevated concentrations of HMOs which 
contains little to no residual lactose through the introduction of lactase which is then removed.  
An unconcentrated, pasteurized form of HMO material containing a proportional amount of lactose 
has already been used in an NIH sponsored clinical trial in premature infants with no reported ill 
effects.v Prolacta Bioscience has also completed a healthy volunteer study using the same HMO 
material as in this trial (with no addition of B. infantis) which showed good tolerability. No treatment 
emergent adverse effects were reported over the course of the trial.6  
The B. infantis preparation being used in this trial is a dietary supplement commercially available in 
the United States and marketed for use in infants. B. infantis is characterized as “generally regarded 
as safe” (GRAS).8  
 
3.1 
THE PURPOSE OF THE ANALYSES 
The primary goal of this study is to evaluate the synergy of PBCLN-005 in varying doses with a 
fixed dose of B. infantis, compared with either component of the IP given alone. Synergy is 
defined as the enhanced gastrointestinal colonization of B. infantis upon feeding with HMO 
feeding. Secondary endpoints will measure changes in the gut microbiome, fecal metabolome 
and the subject’s immune status as measured by systemic markers. We hypothesize that the 
combination will result in greater proliferation of B. infantis than was seen with the HMO 
concentrate alone. 
Another objective is to understand the role of the low pH of the stomach in colonization of B. 
infantis. For most non-spore forming gut bacteria, the stomach is a barrier to colonization since 
acid exposure can reduce bacterial titer by 1,000- to 1,000,000-fold. While most subjects in the 
study will take an over-the-counter proton pump inhibitor (PPI; Zegerid: omeprazole plus 
sodium bicarbonate) to transiently reduce the production of gastric acid prior to B. infantis 
ingestion, one study group will ingest B. infantis without PPI pretreatment. We hypothesize that 
PPI pretreatment is necessary to observe B. infantis colonization. 

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We also hypothesize that ingestion of PBCLN-005 along with the B. infantis will result in a more 
marked change in immune markers than was seen in the previous study in healthy adults. We 
will, therefore, evaluate changes in circulating cytokine and growth factor levels following the 
ingestion of the study compared to baseline levels and between dose groups. 
 
3.2 
STUDY ENDPOINTS 
3.2.1 
Primary 
The primary endpoint will be changes in the level of B. infantis from baseline evaluated by 
quantitative PCR using primers for species and strain. Quantitation limits will be demonstrated 
by qualification assays demonstrating the lower limit of detection, in order to establish minimum 
log-fold change in B. infantis, as it is expected that adult subjects will not harbor B. infantis in 
baseline samples. 
3.2.2 
Secondary  
• Changes in stool microbiota will be measured as well as dynamic changes in the gut 
community structure. These changes will be evaluated by next generation sequencing 
using proportions of key bacterial operational taxonomy units (OTUs), relative 
abundance of various taxa, diversity (alpha and beta) and stability of communities and 
functional metabolomic changes. 
• Changes in viability of proteobacteria and Enterococcus will be determined by plating on 
selective media. These measurements will be predictive for success in suppressing 
pathogenic bacterial relatives in future trials. 
• Blood parameters, such as cytokine levels at study days -1, 8, 15 and 2 except for Cohort 
5 who will also be evaluated on days 36, 43 and 57 
• Determination of the need for protection of B. infantis from stomach acid in order for 
engraftment of the organism into the gut microbiome to occur. 
3.2.3 
Safety 
• Total exposure to the test product will be calculated. 
• Adverse events will be summarized by severity and relationship to study product.  
• The laboratory evaluations listed below will be evaluated for clinical lab and medical 
safety at the following visits: Screening, Day 1, Day 15, Day 29, and, for Cohort 5,  Day 
43 and 57.   
 
o CBC with differential and platelets  

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o Alkaline phosphatase, alanine transaminase (ALT), aspartate transaminase (AST), 
lactate dehydrogenase (LDH), total and conjugated bilirubin, albumin and total 
protein for liver function  
o Electrolytes (Na, K, Cl, and HCO3) 
o Glucose, total calcium, magnesium, phosphate, creatinine, and blood urea 
nitrogen (BUN) for renal function.  
• Vital signs (heart rate, respiratory rate, temperature, and blood press are collected at the 
following visits:  Screening, Day 1, Day 8, Day 15, Day 29, and for Cohort 5, Day 36, 
Day 43, and Day 57.   
o Heart rate 
o Respiratory rate 
o Temperature 
o Blood pressure 
4 
STUDY METHODS 
4.1 
STUDY DESIGN 
 
The study is an unblinded six cohort multi-dose trial using 10 subjects per cohort for a total of 60 
healthy adult volunteers ages 18-75 in order to evaluate the effects of the use of HMO 
Concentrate (PBCLN-005) and B. infantis on the human microbiome. 
 
Six separate cohorts of both male and female study subjects will receive some form of the IP. In 
Cohort 1, the IP will consist of the standard dose of B. infantis alone. In cohort two, the IP will 
consist of only the PBCLN-005. In Cohort groups 3, 4, 5, and 6, the IP will consist of varying 
dose levels of PBCLN-005 together with B. infantis, with each cohort getting a single dose level 
of HMO. In Cohort groups 3, 4, 5, and 6, the IP will contain a standard dose of B. infantis. 
 
Table 1 below summarizes the cohort dosing. 
 
Table 1 Dosing cohorts 
Cohort  
Target HMO Amount  
(days 1-14)  
PPI (days 1-7)  
B. infantis  
(days 1-7)  
1  
None  
Yes, 20 mg  
Yes, one sachet  
2  
18g  
Yes, 20 mg  
None  
3  
4.5g  
Yes, 20 mg  
Yes, one sachet  
4  
9g  
Yes, 20 mg  
Yes, one sachet  
5A  
18g  
Yes, 20 mg  
Yes, one sachet  
6  
18g  
No  
Yes, one sachet  
 

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4.2 
INCLUSION/EXCLUSION CRITERIA AND THE GENERAL 
PATIENT POPULATION 
4.2.1 
Inclusion Criteria 
• Healthy adults between the ages of 18-75 years 
• Willingness to complete study specific questionnaires 
• Willingness to complete journal to record IP dosing times 
• Willingness to complete all study procedures and clinic visits, and provide required 
samples 
• Able to provide stool samples on specific study days 
• 
Willingness to collect and process stool samples at home and transport stool samples to clinic  
• 
Bristol Stool Score of 1 through 5 at time of screening  
• 
Able to store up to 9 days of IP in refrigerator  
• 
Sexually active females of child-bearing potential must agree to use highly effective methods 
of contraception during heterosexual intercourse throughout the study period and for three 
days following discontinuation of PBCLN-005, whichever comes later. Examples of highly 
effective methods include the use of two forms of contraception with one being an effective 
barrier method (e.g., a condom and spermicide used together), or have a vasectomised 
partner. Abstinence is acceptable as a life-style choice. Female subjects who utilize hormonal 
contraceptives as one of their birth control methods must have used the same method for at 
least 3 months before study dosing  
• 
Provides informed consent  
 
4.2.2 
Exclusion Criteria 
• Women who are pregnant or breastfeeding, or intend to become pregnant during the 
course of this study  
• Subjects with allergy to, or other reason for contraindication of the PPI chosen for this 
study.  
• Subjects with history of lactose intolerance  
• Subjects who are on a PPI regimen  
• Subject who has taken a probiotic during the previous 30 days, or intends to take a 
probiotic during the study  
• Subject who has taken antibiotics within 120 days  
• Alcohol or drug abuse during the last 12 months, including passing a screen for drugs of 
abuse at screening  
• Unstable medical condition, in the opinion of the investigator  
• Clinically significant abnormal laboratory test results at screening  
• Subjects who are unable or unwilling to provide stool samples on a regular basis  

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• Participation in a clinical research trial within 30 days prior to screening 
• Unable to give informed consent 
• Any condition which may preclude subject’s ability to comply with and complete the 
study or may pose a risk to the health of the subject. 
• Carriage of B. infantis prior to study start, as determined by qPCR of stool 
• Bristol Stool Score of 6 or 7 at time of screening 
4.3 
RANDOMIZATION AND BLINDING 
 
The study will not utilize randomization or blinding.

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4.4 
SCHEDULE OF EVENTS 
The tables below give the schedule of events for each cohort. 
 
Schedule of Events Table 
Cohort 1 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 1 (Day 0 through Day 29) 
Events 
Cohort 1  
Screening 
Cohort 1  
Dosing Days 
Cohort 1  
Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to 
D1)   
Clinic visit 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Final Visit  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 X 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Review IE Criteria 
X 
X  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Exam 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X  
Demographics (age, 
gender, ethnicity and 
race 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital Signs (Temp, 
BP, pulse, RR) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Height, weight and 
BMI 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prior & Con Meds 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
AEs 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 

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Cohort 1 (Cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 1 (Day 0 through Day 29) 
Events 
Cohort 1 
Screening 
Cohort 1  
Dosing Days 
Cohort 1 
Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to 
D1)   
Randomization 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Dispense IP:   B. infantis 
(≥8x107 cfu/d) and aqueous 
dilute 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dosing: B. infantis (≥8x107 
cfu/d)  
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
Assess IP and Stool 
compliance   
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
 X 
Stool Questionnaires 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Daily Dosing and Flavor 
Questionnaire  
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
Patient Phone Calls 
  
  
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 

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Cohort 1 (Cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 1 (Day 0 through Day 29) 
Events 
Cohort 1  
Screening 
Cohort 1  
Dosing Days 
Cohort 1 
Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to 
D1)   
Urine Drug Screen 
Test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy Test 
(Females of child-
bearing potential) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology &  
Chemistry testing 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
X 
 Immunology testing  
(Screening samples 
will not be evaluated 
for eligibility) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool 
(metagenomics) 
(Screening samples 
will not be evaluated 
for eligibility) 
X 
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Stool (metabolomics) 
(Screening samples 
will not be evaluated 
for eligibility) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool (microbiology) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Fecal pH (using 
nitrazine paper) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 
 

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Schedule of Events Table 
Cohorts 2, 3, 4, and 6 
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 2, 3, 4, & 6 (Day 0 through Day 29) 
Events 
Cohorts 2, 3, 
4, & 6 
Screening 
Cohorts 2, 3, 4, & 6  
Dosing Days 
Cohorts 2, 3, 4, 
& 6 Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to D1)   
Clinic visit 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Final Visit  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 X 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Review IE Criteria 
X 
 X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical Exam 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X  
Demographics (age, 
gender, ethnicity and 
race 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Vital Signs (Temp, 
BP, pulse, RR) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Height, weight and 
BMI 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Prior & Con Meds 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
AEs 
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 
 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 16 of 26 
Cohorts 2, 3, 4, and 6 (cont.) 
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 2, 3, 4 & 6 (Day 0 through Day 29) 
Events 
Cohorts 2, 
3, 4, & 6 
Screening 
Cohorts 2, 3, 4, & 6  
Dosing Days 
Cohorts 2, 3, 
4, & 6  
Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to 
D1)   
Randomization 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Dispense IP:,  B. infantis (≥8x107 
cfu/d) (except Cohort 2) 
(Note: On D1 dispense 9-day 
supply of PBCLN-005.  On D8 
dispense 5-day supply of  PBCLN-
005)  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
Dosing: B. infantis (≥8x107 cfu/d) 
(All Cohorts except Cohort 2) 
  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
Dosing: PBCLN-005 1 bottle po 
bid (Target 4.5g, 9g or 18g)  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
Assess IP and Stool compliance  
 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 Stool Questionnaire  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Daily Dosing and Flavor 
Questionnaire  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
Patient Phone Calls  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
 
 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 17 of 26 
Cohorts 2, 3, 4 & 6 (cont.)  
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 2, 3, 4, & 6  (Day 0 through Day 29) 
Events 
Cohorts 2, 
3, 4, & 6 
Screening 
Cohorts 2, 3, 4, & 6  
Dosing Days 
Cohorts 2, 3, 4, 
& 6 Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
D29 
(+2D) 
(≤ 90 days 
prior to D1)   
Urine Drug Screen Test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy Test 
(Females of child-
bearing potential) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology &  
Chemistry testing 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
X 
Immunology testing  
(Screening samples will 
not be evaluated for 
eligibility)  
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool (metagenomics) 
(Screening samples will 
not be evaluated for 
eligibility) 
X 
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Stool (metabolomics) 
(Screening samples will 
not be evaluated for 
eligibility) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool (microbiology) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Fecal pH (using nitrazine 
paper) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 18 of 26 
 
Protocol Number 20-CT-001 
Schedule of Events For Cohort 5  (Day 0 through Day 22) 
Events 
Cohort 5 
Screening 
Cohort 5  
1st  Dosing Course 
Cohort 5     
1st  Washout 
D0 
D1 
D2 
D3 
D4 
D5 
(+1D) 
D6 
D7 
D8 
(+2D) 
D9 
D10 
D11 
D12 
D13 
D14 
D15 
(+2D) 
D22  
(+2D) 
(≤ 90 days 
prior to D1)   
Urine Drug Screen Test 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Urine Pregnancy Test 
(Females of child-
bearing potential) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology &  
Chemistry testing 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
Immunology testing  
(Screening samples will 
not be evaluated for 
eligibility)  
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Stool (metagenomics) 
(Screening samples will 
not be evaluated for 
eligibility) 
X 
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
X 
X 
Stool (metabolomics)    
(Screening samples will 
not be evaluated for 
eligibility) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Stool (microbiology) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
Fecal pH (using 
nitrazine paper) 
X 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
 
Cohort 5 (cont.) 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 19 of 26 
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 5 Only (Day 29 through Day 57) 
Events 
Cohort 5  
2nd Dosing Course 
Cohort 5  
2nd Washout Period 
D29 
D30 
D31 
D32 
D33 
(+1D) 
D34 
D35 
D36 
(+2D) 
D37 
D38 
D39 
D40 
D41 
D42 
D43 
(+2D) 
D50      
(+2D) 
D57 
(+2D) 
Clinic visit 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Final Visit 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 X 
Physical Exam 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
Vital Signs (Temp, 
BP, pulse, RR) 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Prior & Con Meds 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
AEs 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Dispense IP: PPI(if 
applicable) 1 , B. 
infantis (≥8x107 
cfu/d) 
(Note: On D29 
dispense 9-day 
supply of PBCLN-
005.   
On D36 dispense  
5-day supply of  
PBCLN-005) 
X1 
  
  
  
  
  
  
X1 
  
  
  
  
  
  
  
  
  
Dosing: PPI1  
X1 
X1 
X1 
X1 
X1 
X1 
X1 
  
  
  
  
  
  
  
  
  
  
Dosing: B. infantis 
(≥8x107 cfu/d)  
X 
X 
X 
X 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
Dosing: PBCLN-
005 (Target 18g)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
 
 
 
Cohort 5 (cont.) 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 20 of 26 
Protocol Number 20-CT-001 
Schedule of Events For Cohorts 5 (Day 29 through Day 57) 
Events 
Cohort 5  
2nd Dosing Days 
Cohort 5 
Only 
Washout 
D29 
D30 
D31 
D32 
D33 
(+1D) 
D34 
D35 
D36 
(+2D) 
D37 
D38 
D39 
D40 
D41 
D42 
D43 
(+2D) 
D50 
(+2D) 
D57 
(+2D) 
Assess IP and 
Stool compliance   
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool  
Questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Daily Dosing and 
Flavor 
Questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
Patient Phone 
Calls 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
  
Hematology &  
Chemistry testing 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
X 
Immunology 
testing  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool 
(metagenomics) 
X 
  
  
  
X 
  
  
X 
  
  
  
  
  
  
X 
X 
X 
Stool 
(metabolomics) 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Stool 
(microbiology) 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
Fecal pH (using 
nitrazine paper) 
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
X 
  
X 
 
 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 21 of 26 
4.5 
SAMPLE SIZE 
Six groups of 10 subjects will be included in this study for a total sample size of 60. The sample 
size was not determined statistically, but rather represents a typical number for an exploratory 
study of healthy volunteers.  
4.6 
TIMING OF ANALYSES 
There will be a single analysis of the data at the conclusion of the enrolment of the subjects and 
the collection of the study endpoints 
4.7 
ANALYSIS POPULATIONS 
Since this study is a safety study, the only analytical population will be individuals who receive 
at least one dose of either active drug or placebo. 
4.8 
MISSING DATA 
Investigators should make every effort to ensure that loss to follow-up is kept to a minimum and 
that all data are collected for all subjects at all time points.  However, because this is a Phase 1 
safety study, no data imputation methods will be used to account for missing data. 
4.9 
INTERIM ANALYSES AND DATA MONITORING 
There are no interim analyses conducted during this study.  
5 
SUMMARY OF STUDY DATA 
All continuous variables will be summarized using the following descriptive statistics: n (non-
missing sample size), mean, standard deviation, median, maximum and minimum. The frequency 
and percentages (based on the non-missing sample size) of observed levels will be reported for 
all categorical measures. In general, all data will be listed, sorted by cohort and subject, and 
when appropriate by visit within subjects.  All summary tables will be structured with a column 
for each cohort.   
5.1 
SUBJECT DISPOSITION 
A tabulation of subject disposition will be presented by cohort and overall, including the number 
screened, the number dosed at each level, the number for primary analysis, the number that 
withdrew prior to completing therapy, and reasons for withdrawal. 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 22 of 26 
5.2 
PROTOCOL DEVIATIONS 
Major protocol deviations will be determined at the end of the study when all data have been 
entered into the clinical database.  Protocol violations will be listed by patient.  
5.3 
DEMOGRAPHIC AND BASELINE VARIABLES 
Patient distribution across demographic and baseline characteristics will be tabulated and 
presented by dose group and overall. 
The following demographic and baseline characteristics will be evaluated: 
1) 
Age (calculated as [date of study entry-date of birth]/365.25) 
2) 
Gender 
3) 
Ethnicity 
4) 
Race 
5) 
Physical exam 
o Height 
o Weight 
o BMI 
o Body systems (Normal/Abnormal – clinically significant/Abnormal – not 
clinically significant/Not Done) 
▪ General Appearance 
▪ HEENT 
▪ Heart and cardiovascular 
▪ Dermatologic 
▪ Gastrointestinal 
▪ Musculoskeletal 
▪ Lymphatic 
▪ Neurological 
▪ Respiratory 
6) 
Vital signs 
o Blood pressure  
o Heart rate 
o Respiratory rate 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 23 of 26 
o Temperature 
7) 
Baseline medical history – MedDRA coded and tabulated by system organ class and 
preferred term 
8) 
Baseline laboratory assessments 
6 
 PRIMARY ENDPOINT ANALYSES 
The primary endpoint will be changes in the level of B. infantis from baseline evaluated by 
quantitative PCR using primers for species and strain.  
7 
SECONDARY ENDPOINT ANALYSES 
Since this is an initial study of the use of PBCLN-005 in a clinical population, it is, by definition, 
hypothesis-generating. Therefore, all statistical analyses will be descriptive for the evaluation of 
the data between and within dose groups and the placebo group. 
7.1 
CHANGES IN STOOL MICROBIOTA 
7.1.1 
Fecal Microbial Diversity 
This will include changes in the diversity, composition, and microbial taxa abundance.  
Microbial evenness and richness will be evaluated across all cohorts.   
 
7.2 
CHANGES IN VIABILITY OF PROTEOBACTERIA AND 
ENTEROCOCCUS 
7.3 
CHANGES IN BLOOD PARAMETERS 
7.4 
EVALUATION OF THE USE OF PROTON PUMP INHIBITORS 
FOR PROTECTION OF B. INFANTIS 
8 
SAFETY EVALUATION 
The safety analyses of exposure, AEs and laboratory parameters will include descriptive 
statistics and will be summarized separately by dose group and overall.  Summaries of AEs will 
be generated by type (AE or SAE), body system and preferred term, severity, and relationship to 
study product. 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 24 of 26 
8.1 
ADVERSE EVENTS 
All reported AEs, will be listed, documenting the course, outcome, severity, and causality to 
study drug. Verbatim terms on CRFs will be mapped to preferred terms and related system organ 
class using the Medical Dictionary for Regulatory Activities (MedDRA).  
Incidence rates of AEs and the proportion of subjects prematurely withdrawn from the study due 
to AEs will be shown for all dose groups. Incidence rates will also be displayed based on severity 
and relationship to study drug. AEs with a relationship of “possibly” or “probably” related will 
be considered by the Sponsor as “related” to the study drug. Events assessed as “unrelated”, 
“unlikely” related, or where the relationship was not reported will be considered by the Sponsor 
as “not related” to the study drug. The incidence of SAEs will be provided for each phase. All 
incidence rates will be categorized and displayed by system organ class and preferred term. 
8.2 
CLINICAL LABORATORY EVALUATIONS 
 
The laboratory evaluations listed below will be evaluated for clinical lab and medical safety at 
the following visits: Screening, Day 1, Day 15, and Day 29.  For Cohort 5 only, add Day 43, Day 
57. 
 
• CBC with differential and platelets  
• Alkaline phosphatase, alanine transaminase (ALT), aspartate transaminase (AST), lactate 
dehydrogenase (LDH), total and conjugated bilirubin, albumin and total protein for liver 
function  
• Electrolytes (Na, K, Cl, and HCO3) 
• Glucose, total calcium, magnesium, phosphate, creatinine, and blood urea nitrogen 
(BUN) for renal function.  
 
All laboratory values will be summarized by descriptive statistics; mean ± SD, median ± 
interquartile range along with counts and percentages for categorical data.  
8.3 
VITAL SIGNS 
Vital signs (heart rate, respiratory rate, temperature, and blood pressure) are collected at the 
following visits:  Screening, Day 1, Day 8, Day 15, and Day 29.  For Cohort 5 only, add Day 36, 
Day 43, Day 57. 
 
 Descriptive statistical summaries will be presented by dose group and visit.   
9 
TECHNICAL DETAILS 
All analyses will be conducted using SAS Version 9.4.  MedDRA Version 24.0 will be used to 
code adverse events and medical history conditions. 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 25 of 26 
10 
CHANGES IN CONDUCT OF STUDY OR TO 
PLANNED ANALYSES FROM PROTOCOL 
Deviations from the statistical analyses outlined in this plan will be indicated; any further 
modifications would be noted in the final statistical analysis. 
11 
REFERENCES 
i Barile D, Lebrilla DBC, German B, Rechtman DJ, and Lee ML. Oligosaccharide prebiotics  
present in a breast milk based human milk fortifier. Presented at Hot Topics in Neonatology. 
Washington DC  December 2008 
ii Barile D, German B, Lee ML, and Rechtman DJ. Potential Novel Source for Human Oligosaccharides. Presented 
at American Academy of Pediatrics National Conference and Exhibit, Washington DC 2009. 
 
iii Ninonuevo M., Park Y., YIN H., Zhang J., Ward R.E., Clowers B.H., German J.B., Freeman 
S.L., Killeen K., Grimm R., and Lebrilla C.B.(2006) A strategy to annotate the human milk 
glycome. J.Agric. Food Chem. 54: 7471-7480] 
 
iv Smilowitz JT, Lebrilla CB, Mills DA, German JB, and Freeman SL. Breast Milk 
Oligosaccharides: Structure-Function Relationships in the Neonate. Annu Rev Nutr. 2014 ; 34: 
143–169. 
 
v Underwood MA, Kalanetra KM, Bokulich NA et al. Prebiotic oligosaccharides in premature 
infants. JPGN 2014;58: 352–360 
 
vi Prolacta Bioscience unpublished data on file 
 
7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450358/ 
 
8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114170/ 
 
12 
LISTING OF TABLES, LISTINGS, AND 
FIGURES 
 
TABLES 
Number 
Table Title 
14.1.2 
Summary of Demographics and Baseline Characteristics 

Statistical Analysis Plan 
 
 
Prolacta Bioscience Protocol 20-CT-001 
 04/18/2023 Ver. 1 
CONFIDENTIAL 
Page 26 of 26 
14.1.3 
Summary of Medical History 
14.3.4.1 
Summary of Hematology by Dose Group and Visit 
14.3.4.2 
Summary of Electrolytes/Renal by Dose Group and Visit 
14.3.4.3 
Summary of Liver Serum Analyses by Dose Group and Visit 
14.3.4.4 
Summary of Physical Exams by Dose Group and Visit 
14.3.4.5 
Summary of Vital Signs by Dose Group and Visit 
14.3.4.6  
Summary of Prior and Concomitant Medications 
14.3.1.2 
Number and Percentage of Subjects with Adverse Events by Treatment 
Group, System Organ Class and Preferred Term 
14.3.1.4 
Number and Percentage of Subjects with Adverse Events by Treatment 
Group, System Organ Class, Preferred Term and Relationship to 
Treatment 
14.3.1.5 
Number and Percentage of Subjects with Adverse Events Resulting in 
Withdrawal from Treatment by Treatment Group, System Organ Class, 
and Preferred Term 
14.3.1.6 
Number and Percentage of Subjects with Adverse Events by Treatment 
Group, System Organ Class, Preferred Term, and Severity 
 
LISTINGS 
Number 
Listing Title 
16.2.1.1 
Subject Eligibility 
16.2.2.1 
Subject Disposition 
16.2.2 
Protocol Deviation 
16.2.4.1 
Demographics 
16.2.4.2 
Medical History 
16.2.4.3 
Prior and Concomitant Medications 
16.2.7 
Adverse Events 
16.2.8.1 
Laboratory Results - Hematology 
16.2.8.2 
Laboratory Results – Serum Chemistry 
16.2.8.3 
Laboratory Results – Urinalysis (Drug Screen) 
16.2.8.4 
Laboratory Results – Pregnancy Test 
16.2.8.5 
Vital Signs 
16.2.8.6 
Physical Exams