A Phase 1B Multiple Dose Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Mild-to-Moderate Ulcerative Colitis
Phase: PHASE1
Conditions: Ulcerative Colitis
Sponsor: Seres Therapeutics, Inc.

Clinical Study Protocol 
A Multiple Dose Study to Evaluate the Safety, Tolerability and 
Microbiome Dynamics of SER-287 in Subjects with Mild-to-
Moderate Ulcerative Colitis 
 
Sponsor: 
Seres Therapeutics, Inc. 
200 Sidney Street  
Cambridge, MA 02139 
Clinical Research Organization: 
PAREXEL International 
195 West Street 
Waltham, MA 02451 
 
Sponsor Protocol No.: 
SERES-101 
IND No.: 
16689 
Study Drug Name: 
SER-287 
Development Phase: 
1b 
Date of Protocol Amendment 3: 
10 Oct 2016 
Date of Previous Protocol: 
08 Dec 2015 
The study will be conducted according to the protocol and in compliance with Good 
Clinical Practice (GCP) and with other applicable regulatory requirements. 
This document contains confidential information of Seres Therapeutics, Inc. 
Do not copy or distribute without written permission from the Sponsor. 
CONFIDENTIAL 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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SIGNATURE PAGE 
 
Declaration of Sponsor or Responsible Medical Officer 
Title: A Multiple Dose Study to Evaluate the Safety, Tolerability and Microbiome 
Dynamics of SER-287 in Subjects with Mild-to-Moderate Ulcerative Colitis 
 
This study protocol was subjected to critical review.  The information it contains is 
consistent with current knowledge of the risks and benefits of the investigational product, 
as well as with the moral, ethical, and scientific principles governing clinical research as 
set out in the Declaration of Helsinki, 1989, and the guidelines on Good Clinical 
Practice. 
 
 
_____________________________________ 
_____________________ 
Michele Trucksis, PhD, MD 
Executive Vice President, Chief Medical Officer 
Seres Therapeutics, Inc. 
 
 
10/10/2016

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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Declaration of the Investigator 
Title: A Multiple Dose Study to Evaluate the Safety, Tolerability and Microbiome 
Dynamics of SER-287 in Subjects with Mild-to-Moderate Ulcerative Colitis 
All documentation for this study that is supplied to me, and that has not been previously 
published will be kept in the strictest confidence.  This documentation includes this study 
protocol, Investigator's Brochure, electronic data capture (EDC) system, and other 
scientific data. 
The study will not be commenced without the prior written approval of a properly 
constituted Institutional Review Board (IRB) or Independent Ethics Committee (IEC). 
No changes will be made to the study protocol without the prior written approval of the 
Sponsor and the IRB or IEC, except where necessary to eliminate an immediate hazard to 
the subjects. 
I have read and understood and agree to abide by all the conditions and instructions 
contained in this protocol. 
 
Responsible Investigator of the local study center 
 
 
 
_____________________________________ 
_____________________ 
Signature 
Date 
 
_____________________________________ 
Name (block letters) 
 
_____________________________________ 
Title (block letters) 
 
_____________________________________ 
Institution (block letters) 
 
_____________________________________ 
Phone number 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  4 of 75                                                  10 Oct 2016  
PROTOCOL SYNOPSIS 
Title 
A Multiple Dose Study to Evaluate the Safety, Tolerability and Microbiome 
Dynamics of SER-287 in Subjects with Mild-to-Moderate Ulcerative Colitis 
Sponsor Study No. 
SERES-101 
Phase 
1b 
Sponsor 
Seres Therapeutics, Inc. 
Study Centers 
Approximately 20 Study Centers in the United States (US) 
Objectives 
Primary Objectives:  
•!
To evaluate the safety and tolerability of SER-287 vs. placebo in adult subjects 
≥18 years of age with mild-to-moderate ulcerative colitis 
•!
To compare the baseline composition of the intestinal microbiome to the post-
baseline composition after initiation of SER-287 or placebo  
•!
To determine the engraftment of SER-287 bacteria into the intestinal microbial 
community in each of the SER-287 arms compared to the placebo arm 
Secondary Objectives: 
•!
To determine the proportion of subjects in each of the treatment arms who, at 8 
weeks post initiation of treatment, achieve a clinical response, complete 
remission, and endoscopic improvement 
•!
To assess changes in serum and fecal biomarkers from baseline throughout 
treatment 
Exploratory Objectives:  
•!
To compare the changes in exploratory biomarkers from mucosal biopsies and 
stool samples in each of the treatment arms from baseline throughout treatment. 
•!
To determine the complement of metabolic pathways from stool in each of the 
treatment arms from baseline throughout treatment.  
 
Design 
This is a Phase 1b multicenter, randomized, double-blind, placebo-controlled 
multiple dose study designed to evaluate the safety and tolerability of SER-287, and 
to evaluate the microbiome alterations and pharmacodynamics associated with 2 
dosing regimens of SER-287 in adult subjects with mild-to-moderate ulcerative 
colitis (UC).  Subjects will be randomized to one of 4 study arms: 
Arm A: Placebo pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks 
Arm B: Placebo pre-treatment, followed by once daily placebo for 8 weeks 
Arm C: Vancomycin1 pre-treatment, followed by once daily dosing of SER-287 for 8 weeks 
Arm D: Vancomycin pre-treatment, followed by once weekly dosing of SER-287 for 8 weeks 
 
This study has 5 study periods:  Screening (Day-17 to Day-1), Pre-treatment (Day 
1 to Day 7), 8-Week Treatment (Day 8-63), 4 Week Short Term Safety Follow-up 
(Day 64-92) and a Long Term Safety Follow-up (Day 93-246).   
 
Approximately 55 adult subjects with mild-to-moderate ulcerative colitis will be 
enrolled.   
Screening includes 2 screening visits.  At the first Screening visit, Visit 1, subjects 
will be checked for inclusion /exclusion criteria, and medical history and 
demographic data will be collected.  At the second Screening visit, Visit 2, eligible 
subjects will undergo a lower endoscopy (flexible sigmoidoscopy or colonoscopy) 
and biopsy within 17 days from the first Screening visit and prior to Study Day 1.  
For Baseline Mayo subscore measurement, the one closest to the randomization, 
Visit 2 should be used. 
Subjects will be on a clear liquid diet 1 day before the flexible lower endoscopy 
(flexible sigmoidoscopy or colonoscopy).  On the day of the procedure, the subject 
                                               
1 Full name of Vancomycin is Over-encapsulated (OE) Vancomycin HCl 125 mg capsules  

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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will self-administer a bowel prep at the PI discretion (e.g., 2 Fleets enemas) and fast 
for 6 hours before the procedure.   
Endoscopy images will be obtained during each endoscopy and will be sent for 
independent central reading and determination of the modified Mayo endoscopic 
subscore.  A detailed image review charter from the central reading laboratory will 
outline the endoscopic procedures, video recordings, and equipment to be used for 
video capture and transmission of endoscopic recordings.  For each subject, video 
recording of the entire endoscopic procedure will be performed using a storage 
medium provided by the sponsor or designee.  The endoscopic recordings will be 
read centrally in a blinded manner by a qualified gastroenterologist according to the 
image review charter.  The Total modified Mayo score used for clinical endpoints in 
the trial will use the modified Mayo endoscopic subscore determined by the central 
reader. 
The total modified Mayo score is a composite score, including the modified Mayo 
endoscopic subscore, the patient report outcome (stool frequency and rectal 
bleeding) as well as physician’s rating.  The modified Mayo endoscopic subscore is 
determined by the central reader and provided to the clinical site.  Subjects who 
meet the inclusion criteria (Total modified Mayo score of 4 to 10, inclusive, and 
modified Mayo endoscopic subscore of > 1, with evidence of mucosal lesions), will 
be randomized using an interactive web/voice response system (IxRS) to 1 of 4 
treatment groups on Study Day 1 and initiate the pre-treatment regimen. 
 
During the Pre-Treatment period (Day 1 to Day 7) oral vancomycin 125 mg four 
times a day (qid) or matching placebo will be administered for 6 days.  
Following completion of the Pre-Treatment period, subjects will return to the clinic 
to begin the 8-Week Treatment Period (Day 8-63).  On Day 8, subjects will receive 
SER-287 or placebo according to the Treatment Group to which they have been 
assigned:  SER-287 once daily, SER-287 once weekly with matching placebo on the 
other days, or placebo daily. 
 
During the 8-Week Treatment Period, all subjects will come to the clinic weekly 
for drug dispensing and asked about adverse events (AEs), change in medications 
and the partial Mayo score assessment (scores should reflect the 24-hour period 
prior to reporting).  All subjects will have a lower endoscopy (flexible 
sigmoidoscopy or colonoscopy) at Visit 12/Early Termination +/- 3 days to evaluate 
endoscopic disease activity.  Subjects will be on a clear liquid diet the day before the 
lower endoscopy (flexible sigmoidoscopy or colonoscopy). On the day of the 
procedure, the subject will self-administer a bowel prep at the PI discretion (e.g., 2 
Fleets enemas) and fast for 6 hours before the procedure.   
All subjects will have an in-clinic visit at Visit 12/Early Termination +/- 3 days. 
 
Subjects will then enter the Short-Term Safety Follow-up Period in which 
subjects will be contacted by phone on Days 71, 78, 85 +/- 2 days.  Subjects will be 
asked about adverse events (AEs), concomitant medications and will complete 
disease activity assessment which includes stool frequency and rectal bleeding.  All 
subjects will have an in-clinic safety visit at Visit 13 +/- 2 days.  
 
Subjects will then enter the Long-Term Safety Follow-up Period in which subjects 
will be contacted by phone on Days 246 +/- 3 days. Following Visit 13 through Day 
246/ET only SAEs, and concomitant medications associated with SAEs will be 
collected. 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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Data and Safety 
Monitoring 
Committee 
To ensure safe study conduct during the Phase 1b study, an independent, unblinded, 
external Data and Safety Monitoring Committee (DSMC) will be established to 
perform safety evaluations on an ongoing basis. A DSMC charter will be developed 
and will detail the review of the safety data.  
Treatment 
The Pre-Treatment Period includes administration of either oral vancomycin 125 
mg four times a day (over encapsulated Vancomycin HCl 125 mg) for 6 days or 
matching placebo. 
 
The Treatment Period includes administration of 4 capsules taken orally once daily 
of SER-287 or placebo according to the treatment group to which they have been 
assigned:  SER-287 once daily, SER-287 once weekly with matching placebo on 
other days, or placebo daily. 
 
The doses, route, and schedule of study drug administration are shown below: 
 
Group&
Pre)treatment:&Vanco&or&Pbo&
&&
Treatment&Period:&&SER)287&or&Pbo&
Vanco&
or&Pbo&
Regimen&
Admin&
Duration&
&&
SER6287&
or&Pbo&
Regimen&
Admin&
Duration&
A 
Pbo 
Pbo 
One 
capsule 
four 
times 
daily 
orally 
6 days 
  
SER-
287 + 
Pbo 
SER-287 
Weekly 
(1x108 
SporQs) 
+Pbo 6d/wk 
Four 
capsules 
once 
daily 
orally 
8 wks 
B 
Pbo 
Pbo 
One 
capsule 
four 
times 
daily 
orally  
6 days 
  
Pbo 
Placebo 
Daily 
Four 
capsules 
once 
daily 
orally 
8 wks  
C 
Vanco 
Vanco 
125 mg 
qid 
One 
capsule 
four 
times 
daily 
orally 
6 days 
  
SER-
287  
SER-287 
Daily 
(1x108 
SporQs)   
Four 
capsules 
once 
daily 
orally 
8 wks 
D 
Vanco 
Vanco 
125 mg 
qid 
One 
capsule 
four 
times 
daily 
orally 
6 days 
  
SER-
287 + 
Pbo 
SER-287 
Weekly 
(1x108 
SporQs) 
+Pbo 6d/wk   
Four 
capsules 
once 
daily 
orally 
8 wks 
d = day; Pbo = placebo; qid = Four times a day; wk = week; admin= administration; 
vanco=vancomycin; SporQs= spore equivalents 
 
Number of 
Subjects 
Approximately 55 subjects will be enrolled: 15 subjects in each of the three active 
arms (Groups A, C and D) and 10 subjects in the placebo arm (Group B). 
Population 
Male or female subjects with active mild-to-moderate Ulcerative Colitis ! 18 years 
of age. 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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Criteria for 
Evaluation of 
Efficacy 
The evaluation of the efficacy data will be performed by comparison of the efficacy 
endpoints across treatment arms.  The following efficacy endpoints will be assessed 
for the comparison: 
 
Primary Endpoints 
•!
Composition of the intestinal microbiome  
•!
Engraftment of SER-287 bacteria in all treatment arms 
 
Secondary Endpoints 
•!
Clinical response defined as:  
o!
A decrease of ≥ 3 points in Total Modified Mayo score (TMMS) from 
baseline, along with EITHER a decrease of >1 point in rectal bleeding 
subscore or absolute rectal bleeding subscore of 0 or 1 
•!
Complete remission defined as: 
o!
A Total Modified Mayo Score <2 and an endoscopic subscore 0 with 
no erythema, no blood and no evidence of inflammation  
•!
Endoscopic improvement, defined as a decrease in endoscopic subscore > 1 
•!
Serum biomarkers [C-reactive protein (CRP)] 
•!
Fecal biomarkers (fecal calprotectin) levels 
 
Exploratory Endpoints 
•!
Stool and blood metabolic pathways 
•!
Serum cytokine profile 
•!
Mucosal Histopathology, including cytomegalovirus (CMV) 
Immunohistochemistry stains 
•!
Mucosal microbiome  
•!
Mucosal transcriptomic profile  
•!
Microbial Culture Endpoints: 
o! Candida titer and diversity 
 
Criteria for 
Evaluation of 
Safety 
The evaluation of the safety data will be performed by comparison of the safety 
endpoints across treatment arms.  The following safety parameters will be assessed 
for the comparison: 
•!
Incidence of adverse events 
•!
Incidence of adverse events of special interest 
•!
Laboratory evaluation results 
•!
Vital sign measurements 
•!
Physical examination findings 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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Statistical 
Methods 
All safety and tolerability, intestinal microbiome, clinical efficacy, and biomarker 
data will be listed and presented in descriptive summaries by study arm, visit and 
time point. At a minimum, continuous data will be summarized by study arm using 
descriptive statistics (number, mean, standard deviation [SD], minimum, median and 
maximum).  Categorical data will be summarized by study arm using frequency 
tables (number and percentage). 
 
Analysis Populations 
The Safety Population will consist of all subjects who receive any amount of study 
drug.  Subjects will be analyzed according to the treatment they actually received, 
rather than the treatment to which they were randomly assigned.  All safety analyses 
will be conducted based on the Safety Population. 
 
The Intent-to-Treat (ITT) Population will consist of all subjects who were randomly 
assigned, including those who were not exposed to any study drug, and will be 
analyzed based on the treatment to which they were randomized.   
 
The Modified Intent-to-Treat (mITT) Population will consist of all randomized 
patients with baseline and at least one post-baseline stool sample, including those 
who were not exposed to any study drug, and will be analysed based on the 
treatment to which they were randomized.   
 
All analyses on clinical response will be conducted in the ITT population and in the 
mITT population as sensitivity analyses. 
 
All microbiome alterations analyses will be conducted in the mITT Population. 
 
Analysis of Primary Endpoint 
Adverse Events 
The percentage of subjects with TEAEs will be tabulated by system organ class 
(SOC) and preferred term (PT) for each treatment group. The incidence of TEAEs 
based on the number of days the subjects in each treatment group were on study 
drug (per subject on therapy day) will also be presented by system organ class and 
preferred term for each treatment group, by severity, and by relationship to 
treatment. Tables of any TEAEs leading to study drug discontinuation, AESIs and 
SAEs will also be provided. 
 
Clinical Laboratory Tests 
All scheduled and unscheduled laboratory results will be presented for each subject, 
sorted by category, subject, test and sample time.  Flags will be attached to values 
outside of the laboratory’s reference limits along with the Investigator’s assessment.  
A separate listing of abnormal results will be presented, ordered by test, subject and 
sample time.     
 
Quantitative chemistry and hematology tests (observed values and change from 
baseline) will be summarized descriptively in tabular format. A shift table will be 
presented for chemistry, hematology and urinalysis tests shift from baseline to each 
post-baseline visit and also the shift from baseline to highest and to lowest post-
baseline assessment. 
 
Vital Signs 
Vital signs data include measurements of weight (kg), height (cm), blood pressure 
(mmHg), respiratory rate (breaths/minute), heart rate (bpm), body temperature 
(Celsius / Fahrenheit), and Body Mass Index (kg/m2). Descriptive statistics of the 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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vital signs will be presented by treatment group for all study visits at which they 
were collected. The change from baseline to each post-baseline visit and to the 
overall worst post-baseline value will also be summarized by treatment group. 
 
Physical Examination Findings  
Abnormal clinically significant physical examination (PE) finding will be reported 
as Medical History (MH) or as an AE. 
 
Gastrointestinal tract Microbiome 
The gastrointestinal (GI) microbiome of subjects will be characterized by using at 
minimum recombinant deoxyribonucleic acid (rDNA) 16S V4 genomic data sets 
generated from stool collected for the various endpoints, and may include whole 
metagenome sequence (WMS) characterization. Genomic data sets will define the 
microbial composition of the microbiome of a subject at a given time point. 
Genomic sequence read data sets will be analyzed to assign a taxonomic identity at 
the resolution of an operational taxonomic unit (OTU) and phylogenetic clade 
(clade) and, further, to define the relative proportion of each OTU and clade to all 
other OTUs and clades in a given sample.  
Changes in the composition of the microbiome will be measured in terms of both the 
total number of unique types of bacteria (i.e., α-diversity) and the microbial 
composition (i.e., β-diversity). Engraftment is defined as the outgrowth of bacteria 
that comprise the SER-287 spore ecology in a subject’s gastrointestinal tract post-
treatment. Significant differences between changes in the microbiome across the 
various treatment arms will be evaluated using both non-parametric tests for α-
diversity and multivariate analysis of variances of dissimilarity matrices for β-
diversity. Dissimilarity will be defined by using the unweighted Unifrac 
dissimilarity metric, which evaluates changes in the overall phylogenetic 
composition between two samples; this method is widely used in the study of 
microbial communities and represents a balanced approach with minimal bias to the 
presence of low- and high-abundance bacteria. Additional measures of dissimilarity 
that are routinely used in the analysis of microbiome data sets will be evaluated. 
 
Determination of Sample Size 
No formal sample size calculation was performed.  A sample size of approximately 
55 subjects with 15 subjects randomized to each of the active arms (Treatment 
Groups A, C and D) and 10 subjects in the placebo arm (Treatment Group B) is 
considered sufficient to evaluate the safety, microbiome alterations, clinical response 
and exploratory objectives of the study. 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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LIST OF STUDY PERSONNEL 
 
Sponsor 
Seres Therapeutics, Inc. 
200 Sidney Street 
Cambridge, MA 02139 
 
 
Contract Research 
Organization 
PAREXEL International 
195 West St. 
Waltham, MA 02451 
+1-781-487-9900 
 
Adverse Event Reporting 
PAREXEL International 
1 Federal Street 
Billerica, MA 01821 
Telephone Phone:  +1-781-434-5010 
Fax Number:  +1-781-434-5957 
 
Central Laboratory 
 
Eurofins Central Laboratory 
2430 New Holland Pike 
Lancaster, PA 17601 
 
Central lower endoscopy 
(flexible sigmoidoscopy or 
colonoscopy) Reader 
 
Robarts Clinical Trials  
PO Box 5015  
100 Perth Drive 
London, ON  
CANADA  N6A 5K8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  11 of 75                                                  10 Oct 2016  
Table of Contents 
PROTOCOL&SYNOPSIS&..................................................................................................&4!
List&of&Study&Personnel&..............................................................................................&10!
List&of&Abbreviations&..................................................................................................&14!
1!
Introduction&.......................................................................................................&17!
1.1!
Background&...........................................................................................................&18!
1.1.1!
Brief!Description!of!the!Indication!and!Existing!Practices!......................................!18!
1.1.2!
Rationale!for!the!Development!of!the!Compound,!and!Reasons!why!the!
Investigational!Product!is!Applicable!for!this!Disease!.........................................................!19!
1.1.3!
Pharmacological!Concept!for!the!Treatment!.........................................................!19!
1.1.4!
Name!and!Description!of!Investigational!Product!..................................................!20!
1.1.5!
Summary!of!Findings!from!NonNClinical!Studies!with!Potential!Clinical!Significance
!
20!
1.1.6!
Summary!of!Findings!from!Previous!Clinical!Studies!..............................................!20!
1.2!
Rationale&..............................................................................................................&22!
1.2.1!
Rationale!for!Regimen!............................................................................................!22!
1.2.2!
Rationale!for!dose!...................................................................................................!22!
1.2.3!
Rationale!for!Antibiotic!PreNTreatment!..................................................................!22!
1.2.4!
Rationale!for!Endpoints!..........................................................................................!23!
2!
Study&Objectives&................................................................................................&24!
2.1!
Primary&Objectives&................................................................................................&24!
2.2!
Secondary&Objectives&............................................................................................&24!
3!
Overall&Design&and&Plan&of&the&Study&.................................................................&25!
3.1!
Overview&..............................................................................................................&25!
3.2!
Criteria&for&Evaluation&of&the&Study&.......................................................................&26!
4!
Study&Population&...............................................................................................&28!
4.1!
Inclusion&Criteria&...................................................................................................&28!
4.2!
Exclusion&Criteria&..................................................................................................&28!
4.3!
Subject&Withdrawal&and&Replacement&..................................................................&30!
4.4!
Planned&Sample&Size&and&Number&of&Study&Centers&..............................................&30!
4.5!
Subject&Identification&and&Randomization&.............................................................&31!
4.5.1!
Subject!Identification!..............................................................................................!31!
4.5.2!
Methods!of!Assigning!Patients!to!Study!Treatment!...............................................!31!
4.5.3!
Maintaining!the!Randomization!Codes!and!Breaking!the!Study!Blind!...................!31!
5!
Investigational&Product&......................................................................................&33!
5.1!
SER)287&.................................................................................................................&33!
5.1.1!
Donor!Screening!.....................................................................................................!33!
5.1.2!
SERN287!Manufacturing!..........................................................................................!33!
5.2!
Over)encapsulated&(OE)&Vancomycin&HCl&125&mg&Capsules,&Hard&Gelatin&Capsules&
(“Vancomycin”)&.................................................................................................................&33!
5.2.1!
Vancomycin!HCl!Procurement,!OverNencapsulation,!Packaging!and!Storage!........!33!
5.3!
SER)287&Placebo&Capsules&.....................................................................................&34!
5.3.1!
SERN287!Placebo!Manufacturing!............................................................................!34!

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Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  12 of 75                                                  10 Oct 2016  
5.4!
Vancomycin&HCl&Placebo&Capsules&(“Vancomycin&Placebo”)&..................................&34!
5.4.1!
Vancomycin!HCl!Placebo!Manufacturing!and!Storage!...........................................!34!
5.5!
Storage&.................................................................................................................&34!
5.5.1!
SERN287!and!SERN287!Placebo!Storage!...................................................................!34!
5.6!
Drug&Accountability&..............................................................................................&35!
5.7!
Prior&and&Concomitant&Medications&......................................................................&36!
6!
Variables&and&Methods&of&Assessment&...............................................................&38!
6.1!
Microbiome&Alterations&and&Engraftment&Primary&Endpoints&...............................&38!
6.1.1!
Microbiome!Alterations!..........................................................................................!38!
6.1.2!
Clinical!Response,!Complete!Remission,!and!Endoscopic!Improvement!...............!38!
6.1.3!
Biomarkers!..............................................................................................................!38!
6.2!
Safety&Variables&....................................................................................................&39!
6.2.1!
The!Safety!Endpoints!..............................................................................................!39!
6.2.2!
Adverse!Events!.......................................................................................................!39!
6.2.3!
Laboratory!Variables!...............................................................................................!43!
6.2.4!
Stool!Samples!.........................................................................................................!45!
6.2.5!
Biopsy!Samples!.......................................................................................................!45!
6.2.6!
Vital&Signs!...............................................................................................................!45!
6.2.7!
Electrocardiograms!.................................................................................................!45!
6.2.8!
Physical!Examinations!.............................................................................................!45!
6.3!
Demographics&and&Baseline&Characteristics&...........................................................&46!
6.3.1!
Subject!Demography!..............................................................................................!46!
6.3.2!
Disease!History!.......................................................................................................!46!
6.3.3!
Baseline!Characteristics!..........................................................................................!46!
6.3.4!
Medical!History!.......................................................................................................!46!
6.3.5!
Prior!and!Concomitant!Medications!.......................................................................!46!
7!
Study&Conduct&...................................................................................................&47!
7.1!
Schedule&of&Events&................................................................................................&47!
7.2!
Procedures&by&Visit&...............................................................................................&52!
7.2.1!
Screening!Day!N17!to!Day!N1!(Visit!1)!......................................................................!52!
7.2.2!
Screening!Visit!2!Day!N17!to!Day!N1!(Visit!2)!............................................................!52!
7.2.3!
Pretreatment!Period!Day!1!(Visit!3)!........................................................................!53!
7.2.4!
Treatment!Period!Day!8!±!1!(Visit!4)!.......................................................................!53!
7.2.5!
Treatment!Period!Day!11!(as!close!to!scheduled!day!as!possible)!.........................!54!
7.2.6!
Treatment!Period!Day!15!±!1!(Visit!5)!.....................................................................!54!
7.2.7!
Treatment!Period!Day!18!(as!close!to!scheduled!day!as!possible)!.........................!54!
7.2.8!
Treatment!Period!Day!22!±!1!(Visit!6)!.....................................................................!54!
7.2.9!
Treatment!Period!Day!29!±!1!(Visit!7)!.....................................................................!55!
7.2.10!
Treatment!Period!Day!36!±!1!(Visit!8)!................................................................!55!
7.2.11!
Treatment!Period!Day!43!±!1!(Visit!9)!................................................................!55!
7.2.12!
Treatment!Period!Day!50!±!1!(Visit!10)!..............................................................!55!
7.2.13!
Treatment!Period!Day!57!±!1!(Visit!11)!..............................................................!56!
7.2.14!
FollowNup!Period!Day!64!±!3!(Visit!12)/Early!Termination!.................................!56!
7.2.15!
FollowNup!Period!Day!71!±!2!(Phone!Call)!..........................................................!57!
7.2.16!
FollowNup!Period!Day!78!±!2!(Phone!Call)!..........................................................!57!
7.2.17!
FollowNup!Period!Day!85!±!2!(Phone!Call)!..........................................................!57!
7.2.18!
FollowNup!Period!Day!92!±!1!(Visit!13)!...............................................................!57!

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7.2.19!
Early!Termination!Visit!.......................................................................................!57!
7.2.20!
FollowNup!Period!Day!246!±!3!(Phone!Call)!........................................................!57!
8!
Statistical&Methods&............................................................................................&59!
8.1!
Study&Subjects&......................................................................................................&59!
8.1.1!
Disposition!of!Subjects!...........................................................................................!59!
8.1.2!
Protocol!Deviations!................................................................................................!59!
8.1.3!
Analysis!Sets!...........................................................................................................!59!
8.2!
Endpoints&for&Analysis&...........................................................................................&60!
8.2.1!
Endpoints!and!Analysis!for!Primary!Objectives!......................................................!60!
8.2.2!
Endpoints!and!Analysis!for!Secondary!Objectives!..................................................!60!
8.2.3!
Exploratory!Endpoints!............................................................................................!60!
8.3!
General&Considerations&.........................................................................................&61!
8.3.1!
Statistical!Methods!.................................................................................................!61!
8.3.2!
Statistical!Significance!............................................................................................!61!
8.3.3!
Missing!or!Spurious!Data!........................................................................................!61!
8.4!
Safety&Analyses&.....................................................................................................&62!
8.4.1!
Adverse!Events!.......................................................................................................!62!
8.4.2!
Clinical!Laboratory!Tests!.........................................................................................!62!
8.4.3!
Vital!Signs!...............................................................................................................!62!
8.4.4!
Physical!Examination!Findings!................................................................................!62!
8.4.5!
Pharmacokinetic!Analyses!......................................................................................!62!
8.5!
Gastrointestinal&Tract&Microbiome&........................................................................&62!
8.6!
Interim&Analyses&...................................................................................................&63!
8.7!
Determination&of&Sample&Size&...............................................................................&63!
9!
ADMINISTRATIVE&REQUIREMENTS&.....................................................................&64!
9.1!
Good&Clinical&Practice&............................................................................................&64!
9.2!
Ethical&Considerations&...........................................................................................&64!
9.3!
Subject&Information&and&Informed&Consent&...........................................................&64!
9.4!
Subject&Confidentiality&..........................................................................................&65!
9.5!
Protocol&Compliance&.............................................................................................&65!
9.6!
Future&Use&of&Stored&Specimens&............................................................................&65!
9.7!
Study&Monitoring&..................................................................................................&65!
9.8!
Data&and&Safety&Monitoring&Committee&................................................................&66!
9.9!
Case&Report&Forms&and&Study&Records&..................................................................&66!
9.10!
Study&Completion&.................................................................................................&67!
10! Reference&List&....................................................................................................&68!
Appendices&...............................................................................................................&72!
 
Tables in Text 
Table 1: Doses, Route, and Schedule of Study Drug Administration ........................35!
Table 2: Laboratory Assessments ...............................................................................44!
Table 3: Schedule of Events .......................................................................................48!
 
 
 

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List of Abbreviations 
 
Abx 
Antibiotic 
AE 
AESI 
Adverse event 
Adverse Event of Special Interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
ANOVA 
Analysis of variance 
5-ASA 
Aminosalicylate 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical [Classification System] 
BP 
Blood pressure 
Bpm 
Beats per minute 
CDI 
Clostridium difficile infection 
CFR 
Code of Federal Regulations 
Cm 
Centimeter 
CMV 
Cytomegalovirus 
CS 
Clinically significant 
Cx 
Culture 
D 
Day 
DNA 
Deoxyribonucleic acid 
DRL 
Drug Reference List 
DSMC 
Data and Safety Monitoring Committee 
DSS 
Dextran sodium sulfate 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
CRP 
C-reactive protein 

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EDC 
Electronic data capture 
ESR 
Erythrocyte sedimentation rate 
FMT 
Fecal microbiota transplantation 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transpeptidase 
GI 
Gastrointestinal 
HDPE 
High density polyethylene 
HR 
Heart rate 
IBD 
Inflammatory bowel disease 
ICF 
Informed consent form 
IEC 
Independent Ethics Committee 
ICH 
International Conference on Harmonization 
IMP 
Investigational medical product 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat; intention-to-treat 
IVR 
Interactive voice response 
IxRS 
Interactive web/voice response system 
Kg 
Kilogram 
LFT 
Liver function test 
MCH 
Mean corpuscular hemoglobin 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MH 
Medical history 
mL 
Milliliter 
mmHg 
Millimeters of mercury 
MMX 
Multi-matrix system 
NCS 
Not clinically significant 
NSAID 
Non-steroidal anti-inflammatory 
OE 
Overencapsulated 
OTU 
Operational taxonomic unit 
Pbo 
Placebo 

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PBS 
Phosphate buffered saline 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
PE 
Physical examination 
PI 
Principal Investigator 
PT 
Preferred term 
qid 
Four times a day 
rDNA 
Recombinant deoxyribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCFU 
Spore Colony Forming Unit 
SD 
Standard deviation 
SID 
Subject identification 
SOC 
System organ class 
SPF 
Specific Pathogen Free 
SporQ 
Spore Equivalents, a dosing unit measured by dipicolinic acid content 
TEAE 
Treatment-emergent adverse event 
TMMS 
Total modified Mayo score 
TNBS 
2,4,6-Trinitrobenzenesulfonic acid 
Tregs 
Regulatory T cells 
UC 
Ulcerative colitis 
ULN 
Upper limit of normal 
US 
United States 
Wk 
Week 
WHO 
World Health Organization 
WOCBP 
Women of child bearing potential 
 
 

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1!
INTRODUCTION 
Ulcerative colitis (UC) is a relapsing-remitting chronic inflammatory disorder affecting 
the mucosal surface of the colon, leading to episodes of bloody diarrhea, urgency and 
mucosal inflammation.(Danese and Fiocchi, 2011)  As the disease mostly affects young 
and middle-aged individuals, the disease leads to decreased quality of life in those 
affected by the condition, high morbidity and significant economic burden accounting for 
nearly four billion health care dollars annually.(Ghosh and Mitchell, 2007; Kappelman et 
al., 2008; Rubin et al., 2014; Theede et al., 2015)  Current medical therapies remain 
imperfect for the treatment of UC with the focus of drug development on suppressing the 
immune system rather than reducing the triggers of immune activation.  As 
immunosuppressive agents increase the risk of infectious and oncologic complications, 
alternative mechanisms of action to decrease immune activation, remain attractive 
therapeutic goals for UC.  
The prevailing model of disease pathogenesis for UC is that in the genetically 
predisposed host, environmental factors are sufficient to generate an abnormally 
perpetuated immune response and inflammation.(Xavier and Podolsky, 2007)  
Alterations in the intestinal microbiota parallel changes in environmental factors with 
evidence suggesting a role of the intestinal microbiota in immune modulation. 
(Biedermann et al., 2013, 2014; Leone et al., 2013; Wu et al., 2013) Studies suggest that 
the intestinal microbiome of UC patients is characterized by a decrease in microbial 
diversity and richness, with a lower prevalence of organisms within the phylum, 
Firmicutes. (Frank et al., 2007; Lepage et al., 2011; Machiels et al., 2014; Michail et al., 
2012; Morgan et al., 2012; Ott et al., 2004; Papa et al., 2012; Rajilić-Stojanović et al., 
2013; Sartor, 2008; Varela et al., 2013; Walujkar et al., 2014; Willing et al., 2010)   
Given the dysbiosis seen in UC patients, studies have explored the use of fecal microbial 
transplantation (FMT) to treat UC.  Two randomized, double-blind, placebo-controlled 
studies suggest a clinical response in mild-to-moderate UC patients by repopulating the 
intestinal microbial flora via FMT with that of a healthy donor (Moayyedi et al., 2015; 
Rossen et al., 2015). There was increased microbial diversity and greater similarity to 
donor microbiota profile noted in subjects with a clinical response to FMT in both 
studies suggesting that changes in the microbiome due to FMT were responsible for this 
clinical response.  This study will explore microbial therapeutic interventions and the 
impact on the disease course in UC.  The study hypothesis is that SER-287, enriched in 
spore-forming organisms that are diminished in active UC, can induce remission in mild-
to-moderate ulcerative colitis.   
SER-287 (Eubacterial Spores, Purified Suspension, Encapsulated) is an ecology of 
bacterial spores enriched from fecal donations obtained from healthy, screened donors. 
Bacterial spores are enriched by thorough killing of the vegetative microorganisms with 
ethanol, and then purifying and formulating the resulting spore population.  SER-287 is 
delivered as oral capsules for administration to patients.    
SER-287 for this Phase 1b clinical study was manufactured as SER-109 and then became 
SER-287 at the time of clinical labeling. SER-109 was administered in a Phase 1b/2 

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study (SERES-001), and was shown to increase bacterial diversity of the gut microbiota 
as early as 4 days after dosing in adults with recurrent Clostridium difficile infection 
(CDI). Currently there are no differences in the drug products, SER-109 and SER-287.  
Seres anticipates that, pending results from this Phase 1b clinical study, there may be 
future changes in SER-287, with respect to dose, formulation and/or regimen during 
development.!
The patient population targeted for inclusion in this study is adults !18 years of age who 
have mild-to-moderate ulcerative colitis, as defined by a Total Modified Mayo score 
between 4 and 10, inclusive, with a Modified Mayo endoscopic subscore > 1.   
The primary objective of this study is to assess the safety and tolerability of SER-287 in 
patients with active mild-to-moderate ulcerative colitis.  In addition, the study will 
evaluate the microbiome dynamics throughout treatment and assess preliminary efficacy 
data.  
1.1!
Background 
1.1.1! Brief Description of the Indication and Existing Practices  
The annual incidence rate of UC in Western countries is roughly 9.8/100,000 person-
years with increasing incidence observed in developing countries.(Grinspan and 
Kornbluth, 2015) Approximately 50% of patients experience proctosigmoiditis, 30% 
have left-sided disease, and 20% have pancolitis. (Kothari et al., 2015) Overall, 
approximately 50% develop more extensive disease over the first 5 years of disease. 
There is currently no cure for UC.  Therefore, the therapeutic goal is to alleviate and 
control symptoms (induction of remission) and to promote mucosal healing but also to 
prevent disease recurrence (maintenance of remission). 
Current medical therapies for UC include sulfasalazine, aminosalicylates (5-ASAs), 
steroids, immunomodulators (azathioprine and 6-mercaptopurine), anti-TNF agents 
(infliximab, adalimumab, golimumab), anti-integrin agents (vedolizumab), and 
calcineurin inhibitors (cyclosporine and tacrolimus).(Grinspan and Kornbluth, 2015)  As 
the majority of these medications are immunosuppressant agents targeted for moderate-
to-severe disease, there remains an unmet need for safer agents with novel mechanisms 
of action, especially for patients with mild-to-moderate UC who experience frequent 
flares on aminosalicylates or as an alternative to aminosalicylate therapy in those 
intolerant to this class of medication.  As alterations in the intestinal microbiome have 
been identified in UC and preliminary evidence suggests that microbial interventions can 
affect clinical outcomes, the study will assess whether an ecology of bacterial spores 
devoid of vegetative organisms in SER-287 can correct the dysbiosis in UC, increase 
microbial diversity and lead to clinical response in UC patients with active mild-to-
moderate disease.   
 

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1.1.2! Rationale for the Development of the Compound, and Reasons why the 
Investigational Product is Applicable for this Disease 
The intestinal microbiome is comprised of four principle bacterial phyla: Bacteroidetes, 
Firmicutes, Actinobacteria and Proteobacteria.  In healthy subjects, the intestinal 
microbiome is mainly composed of Bacteroidetes and Firmicutes.(Human Microbiome 
Project Consortium, 2012)  Studies have shown that subjects with inflammatory bowel 
disease, including UC, have a decrease in bacterial diversity and alterations in the 
intestinal microbiota compared to healthy subjects.(Baumgart et al., 2007; Frank et al., 
2007; Gevers et al., 2014; Lepage et al., 2011; Machiels et al., 2014; Michail et al., 2012; 
Morgan et al., 2012; Ott et al., 2004; Papa et al., 2012; Rajilić-Stojanović et al., 2013; 
Sartor, 2008; Sokol et al., 2008; Varela et al., 2013; Walujkar et al., 2014; Willing et al., 
2010)   
The dysbiosis described in UC is characterized by lower microbial diversity and species 
richness, a greater prevalence of organisms within the phylum, Proteobacteria, and a 
lower prevalence of commensal bacteria within the phylum, Firmicutes.  (Frank et al., 
2007; Lepage et al., 2011; Machiels et al., 2014; Michail et al., 2012; Ott et al., 2004; 
Rajilić-Stojanović et al., 2013; Varela et al., 2013; Walujkar et al., 2014) In particular, 
Firmicutes within the Clostridiales order are poorly represented in active UC subjects 
than in age and sex-matched healthy controls with an inverse correlation between disease 
activity and presence of these organisms.(Michail et al., 2012)  This study will test the 
hypothesis that administering bacterial spores comprised of predominantly Clostridial 
commensals within SER-287 to UC patients can help correct the dysbiosis and improve 
clinical outcomes.      
1.1.3! Pharmacological Concept for the Treatment 
Given the dysbiosis seen in UC patients, studies have explored the use of fecal microbial 
transplantation to treat UC. (Angelberger et al., 2013; Colman and Rubin, 2014; Kump et 
al., 2013; Kunde et al., 2013; Moayyedi et al., 2015; Rossen et al., 2015)  Fecal microbial 
transplantation (FMT) is the transfer of stool from a healthy donor to a recipient.  FMT 
has already demonstrated efficacy in preventing recurrent Clostridium difficile infection 
(CDI) with response corresponding to shifts of the recipient’s flora towards that of the 
donor’s and increasing microbial diversity in the recipient’s microbiome. (van Nood et 
al., 2013; Youngster et al., 2014a, 2014b)  
Most recently, two randomized controlled trials have evaluated the role of FMT in UC.  
One study administered FMT via enema weekly over 6 weeks (treatment group) versus 
water enemas (control group) to 75 patients with mild-to-moderate UC with the primary 
endpoint of clinical remission achieved in 24% of patients in the treatment group and 5% 
in the control group (p=0.03).(Moayyedi et al., 2015) Clinical remission was defined as a 
Mayo score < 3 with an endoscopic subscore of 0 at week 7.  In a second study, donor 
FMT (treatment group) or autologous FMT (control group) was administered twice (3 
weeks apart) via nasoduodenal tube to 50 UC patients with mild-to-moderate ulcerative 
colitis. (Rossen et al., 2015) After 12 weeks, while there was no significant difference in 
clinical remission between groups, there was a trend towards response in the treatment 
group (30.4% versus 20% control group, p=0.51) and there was increased microbial 

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diversity noted in responders of both groups with responders in the treatment group 
developing a similar microbiota profile to the donor.  Given these findings of treatment 
response to FMT in UC patients, this study will explore further if supplementing the 
microbiome of UC patients with select spore-forming organisms in SER-287, that are 
underrepresented in subjects with active ulcerative colitis, could alter the microbiome of 
the recipient and lead to improved clinical outcomes. 
1.1.4! Name and Description of Investigational Product 
SER-287 (Purified Eubacterial Spores, Encapsulated) is an ecology of bacterial spores 
enriched from fecal donations obtained from healthy, screened donors, representing 
approximately 50 commensal bacteria in spore form. The bacterial spores are enriched by 
thorough killing of the vegetative microorganisms, then fractionating the resulting spore 
population away from the inactive components and formulating and encapsulating the 
spores for oral delivery.  SER-287 for the proposed Phase 1b clinical study will be 
manufactured as SER-109. Currently, there are no differences between SER-109 and 
SER-287. Seres anticipates that, pending results from the Phase 1b clinical study, there 
may be future changes in SER-287, with respect to dose, formulation and/or regimen 
during development. 
1.1.5! Summary of Findings from Non-Clinical Studies with Potential Clinical 
Significance  
Recent evidence has identified dysbiosis of the intestinal microbiome as a contributing 
factor to the pathology in UC. Preclinical evidence in mice supports that, more 
specifically, the spore-forming fraction of both murine and human fecal microbiota is 
sufficient to drive protection against experimental colitis, in part via the induction of 
regulatory T cells (Tregs) in the colon (Atarashi et al., 2011, 2013).  
In light of these data, efficacy of a research preparation of SER-287, comprised 
predominantly of Clostridial spore-forming organisms, was evaluated in pilot studies 
using mouse models of colitis [2,4,6-trinitrobenzenesulfonic acid (TNBS) and dextran 
sodium sulfate (DSS)]. In these experimental models of colitis, antibiotic pre-treatment 
with SER-287 (Abx + SER-287) improved clinical outcomes in the DSS model (Further 
details can be found in the Investigator's Brochure). These data support the hypothesis 
that SER-287, in combination with antibiotic pre-treatment, may improve symptoms of 
ulcerative colitis in man. 
1.1.6! Summary of Findings from Previous Clinical Studies  
SERES-101 will be the first study investigating the use of SER-287 in ulcerative colitis.  
At this time, there are no differences between SER-109 and SER-287 but SERES 
anticipates future changes in the dose, frequency and formulation of SER-287 in UC.  
Data from a SER-109 clinical study (SERES-001) in prevention of recurrent Clostridium 
difficile infection (CDI) provides data on SER-109 safety and post-treatment microbiome 
dynamics. SERES-001 has been completed and two additional clinical studies are 
ongoing: 

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•! A Phase 1/2 Study (SERES-001: A Study of Modified Fecal Microbiota 
Transplant [SER-109] Delivered via Oral Administration for the Treatment of 
Recurrent Clostridium difficile) - completed 
•! A Phase 2 Study (SERES-004 ECOSPOR: A Randomized, Double-Blind,  
Placebo-Controlled, Parallel-Group Study of SER-109 to Prevent Recurrent  
Clostridium difficile Infection) - ongoing 
•! An Extension Study to the Phase 2 Study (SERES-005 ECOSPOR II: An Open- 
Labeled Extension of Studies SERES-004/SERES-007 Evaluating SER-109 in  
Patients with Recurrent Clostridium difficile Infection) – ongoing 
Further details can be found in the Investigator's Brochure. 
SERES-001 was an open-label, single arm, descending-dose study that evaluated the 
safety and efficacy of SER-109 in prevention of recurrent CDI in adult patients with a 
history of recurrent CDI episodes, a condition in which the microbiome is characterized 
as a low diversity state. Thirty patients were enrolled following a therapeutic response to 
standard of care CDI antibiotics. The primary endpoint of absence of diarrhea with a 
positive C. difficile test up to 8 weeks following dosing was achieved in 26 (87%) 
patients.  Furthermore, evaluation of the microbiome pre- and post-treatment showed 
SER-109 increased bacterial diversity of the intestinal microbiota as early as 4 days after 
dosing. SER-109 in SERES-001 was safe and tolerable with no deaths. Seven SAEs were 
reported in 4 subjects, none considered related to SER-109.   
Similar to CDI, UC is characterized by a decrease in microbial diversity and richness, 
with a lower prevalence of spore-forming organisms within the phylum, Firmicutes. The 
results from the SERES-001 study in recurrent CDI support exploration of the efficacy of 
SER-287 in increasing bacterial diversity of the intestinal microbiota in UC patients. The 
study population in SERES-001 was older (mean age of 62 years) with frequent co-
morbid illnesses than what is anticipated for the UC population.  Therefore, we anticipate 
a high safety profile in the UC population.  However, as the population will be different 
for this Phase 1b study (SERES-101) than for SERES-001, SERES-101 will evaluate the 
safety, tolerability and microbiome dynamics of SER-287 in UC patients.  
SERES-101 is a Phase 1b multicenter, randomized, double-blind, placebo-controlled 
multiple dose study designed to evaluate the safety and tolerability of SER-287 and to 
evaluate the microbiome alterations and pharmacodynamics associated with two dosing 
regimens of SER-287 in adult subjects with mild-to-moderate UC. Subjects will be 
randomized to one of 4 study arms:  A) Pre-treatment of placebo, followed by weekly 
dosing of SER-287 for 8 weeks, B) Pre-treatment of placebo, followed by daily dosing of 
placebo for 8 weeks. C) Pre-treatment of vancomycin, followed by daily dosing of SER-
287 for 8 weeks, D) Pre-treatment of vancomycin, followed by weekly dosing of SER-
287 for 8 weeks. From screening to last follow-up, the study duration will be between 
35-37 weeks.  

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1.2!
Rationale 
SER-287 (Purified Eubacterial Spores, Encapsulated) is an ecology of bacterial spores 
enriched from fecal donations obtained from healthy, screened donors, representing 
approximately 50 commensal bacteria in spore form.  As UC is characterized by a 
decrease in microbial diversity and richness, with a lower prevalence of spore-forming 
organisms within the phylum, Firmicutes, and preliminary evidence suggests that 
microbial interventions can affect clinical outcomes in UC, the study will examine 
whether SER-287 can correct the dysbiosis in UC, increase microbial diversity and lead 
to clinical response in UC patients with mild-to-moderate disease.   
1.2.1! Rationale for Regimen  
The inflammatory milieu in UC impacts the microbial composition with animal and 
human studies showing a greater representation of Enterobacteriaceae with a relative 
depletion of Clostridial organisms. This dysbiosis is seen in patients with recurrent CDI 
and can be reversed after FMT. While the dysbiosis in Clostridium difficile is mainly 
induced by infection, toxin production and repeated antibiotic usage, the dysbiosis in UC 
is more complex with host factors and alterations in microbial-host interactions likely 
contributing to the witnessed microbial changes.  
This study will evaluate whether repeated dosing can alter the microbial community in 
UC, encourage engraftment and, ultimately, decrease mucosal inflammation.  This study 
will test the weekly dosing strategy that was evaluated in the study by Moayyedi et al. 
and will also evaluate a daily dosing strategy.(Moayyedi et al., 2015) Given that the aim 
of the study is to induce remission in patients with active mild-to-moderate 
inflammation, this study will evaluate a higher frequency of dosing from weekly to daily 
dosing of SER-287 to provide consistent and maximal exposure to SER-287 treatment 
during a period of active inflammation. 
1.2.2! Rationale for dose  
The dose selected in this study is supported by the safety and effectiveness of this dose, 
[1 x 108 Spore Equivalents (SporQs)], administered in the SER-109 Phase 1b/2 study for 
recurrent CDI. The trial explored a range of doses from 3.4"107 to 2.3"1010 SporQs.  The 
doses evaluated were safe with no deaths in the study and no concerning trends in 
laboratory values, vital signs or physical examination findings. The SAEs reported were 
deemed by the investigators to not be related to SER-109.  
The dose selected gives a 230-fold margin to the highest dose tested in SERES-001 and a 
3-fold margin to the lowest dose shown to be effective in SERES-001. Although the 
study population for SERES-001 is not the same study population targeted for the current 
study, the study population in SERES-001 is older (mean age of 62 years) with frequent 
co-morbid illnesses than the general UC population.  
1.2.3! Rationale for Antibiotic Pre-Treatment 
Disease states, such as CDI and UC, are characterized by intestinal dysbiosis and a 
decrease in microbial diversity. Antibiotic treatment prior to administration of a 
repopulating ecology of spores (SER-287) may allow for engraftment of the spores 
administered.  Data described in the DSS animal colitis models with SER-287 

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demonstrate a trend toward improvement by the addition of antibiotics prior to SER-287 
administration (see Investigator’s Brochure).  
Data from the SERES-001 study in prevention of recurrent CDI showed engraftment of 
bacteria from SER-109 as early as 4 days following SER-109 dosing. All the subjects in 
this study were pre-treated with antibiotics prior to SER-109 dosing, supporting, 
although not proving, that antibiotic pre-treatment may enhance engraftment. This study 
will assess whether vancomycin improves engraftment and clinical outcomes through a 
comparison of outcomes in arms with and without vancomycin pre-treatment. 
1.2.4! Rationale for Endpoints  
Efficacy endpoints will be measured incorporating an accepted clinical and endoscopic 
disease activity index in UC, the Total modified Mayo score, with an 8-week treatment 
period to evaluate induction of remission for UC in keeping with FDA regulatory 
guidance. The study will also evaluate endoscopic disease activity before and after 
treatment via central reading.  Clinical disease activity throughout the study will be 
monitored via the partial Mayo score, which is the Mayo Score without the endoscopic 
subscore.   Definitions of disease activity are defined by prior studies for the mild-to-
moderate UC population.(Lichtenstein et al., 2015; Moayyedi et al., 2015; Sandborn et 
al., 2015)  
This study is designed to also evaluate microbiome changes in this Phase 1b study. 
Engraftment is defined as the outgrowth of bacteria that comprise the SER-287 ecology 
in a patient’s gastrointestinal tract post-treatment.  This study will evaluate the 
engraftment of SER-287 bacterial isolates in each treatment arm and determine the 
overall change in composition of the microbiome both by total number of unique types of 
bacteria (ie, α-diversity) and by microbial composition (ie, β-diversity).  The dysbiosis 
described in IBD is characterized by lower microbial diversity and species richness, a 
greater prevalence of pro-inflammatory pathobionts, mainly described within the 
phylum, Proteobacteria, and a lower prevalence of commensal bacteria within the 
phylum, Firmicutes, of which the Clostridial organisms within SER-287 belong.  

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2!
STUDY OBJECTIVES 
2.1!
Primary Objectives 
•! To evaluate the safety and tolerability of SER-287 vs. placebo in adult subjects !18 
years of age with mild-to-moderate ulcerative colitis 
•! To compare the baseline composition of the intestinal microbiome to the post-
baseline composition after initiation of SER-287 or placebo  
•! To determine the engraftment of SER-287 bacteria into the intestinal microbial 
community in each of the SER-287 arms compared to the placebo arm 
2.2!
Secondary Objectives 
•! To determine the proportion of subjects in each of the treatment arms who, at 8 
weeks post initiation of treatment, achieve a clinical response, complete remission, 
and endoscopic improvement 
•! To assess changes in serum and fecal biomarkers from baseline throughout treatment 
 
2.3 Exploratory Objectives 
•! To compare the changes in exploratory biomarkers from mucosal biopsies and stool 
samples in each of the treatment arms from baseline throughout treatment.  
•! To determine the complement of metabolic pathways from stool in each of the 
treatment arms from baseline throughout treatment. 
 
 

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3!
OVERALL DESIGN AND PLAN OF THE STUDY 
3.1!
Overview 
This is a Phase 1b multicenter, randomized, double-blind, placebo-controlled multiple 
dose study designed to evaluate the safety and tolerability of SER-287 and to evaluate the 
microbiome alterations and pharmacodynamics associated with two dosing regimens of 
SER-287 in adult subjects with mild-to-moderate UC. Subjects will be randomized to 
one of 4 study arms: A) Pre-treatment of placebo, followed by weekly dosing of SER-
287 for 8 weeks; B) Pre-treatment of placebo, followed by daily dosing of placebo for 8 
weeks; C) Pre-treatment of vancomycin, followed by daily dosing of SER-287 for 8 
weeks; D) Pre-treatment of vancomycin, followed by weekly dosing of SER-287 for 8 
weeks.  
 
The study is broken down into 5 study periods:  Screening (Day-17 to Day-1), Pre-
treatment, (Day 1 to Day 7), 8-Week Treatment Period (Day 8-63), a 4-Week Short 
Term Safety Follow-up Period (Day 64-92) and a Long Term Safety Follow-up Day 93 -
246).  Approximately 55 adult subjects with mild-to-moderate ulcerative colitis will be 
enrolled.   
 
Screening includes 2 screening visits.  At the first Screening Visit, (Visit 1), subjects 
will be checked for inclusion/exclusion criteria, and medical history and demographic 
data will be collected.  At the second Screening Visit, (Visit 2) eligible subjects will 
undergo a lower endoscopy (flexible sigmoidoscopy or colonoscopy) and biopsy within 
17 days from the Screening visit and prior to Study Day 1.  Subjects will be on a clear 
liquid diet 1 day before the lower endoscopy (flexible sigmoidoscopy or colonoscopy). 
On the day of the procedure, the subject will administer a bowel prep at the PI discretion 
(e.g., 2 Fleets enemas) and fast for 6 hours before the procedure.   
  
Endoscopy images will be obtained during each endoscopy and will be sent for 
independent central reading and determination of the modified Mayo endoscopic 
subscore. A detailed image review charter from the central reading laboratory will 
outline the endoscopic procedures, video recordings, and equipment to be used for video 
capture and transmission of endoscopic recordings. For each subject, video recording of 
the entire endoscopic procedure will be performed using a storage medium provided by 
the sponsor or designee. The endoscopic recordings will be read centrally in a blinded 
manner by a qualified gastroenterologist according to the image review charter. The 
modified Mayo score used for clinical endpoints in the trial will use the modified Mayo 
endoscopy subscore determined by the central reader. 
! 
The Total modified Mayo score is a composite score.  Only the modified Mayo 
endoscopic subscore is determined by central reader and provided to the clinical site.  If 
the partial Mayo score changes from Visit 1 to Visit 2, the Visit 2 score should be used in 
computing the Total modified Mayo score at Baseline and when assessing the subject for 
the safety stopping rules. Subjects who meet the inclusion criteria (Total modified Mayo 
score of 4 to 10, inclusive and modified Mayo endoscopic subscore of > 1, with evidence 

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of mucosal lesions), will be randomized using an interactive web/voice response system 
(IxRS) to 1 of 4 treatment groups on Study Day 1 and initiate the pre-treatment regimen. 
 
During the Pre-Treatment period (Day 1 to Day 7) oral vancomycin 125 mg four times 
a day (qid) or matching placebo will be administered for 6 days.  
 
During the 8-Week Treatment Period, all subjects will come to the clinic weekly for 
drug dispensing and asked about adverse events (AEs), change in medications and the 
partial Mayo score assessment (scores should reflect the 24-hour period prior to 
reporting.  The endoscopy procedure day or preparation day should not be included).  All 
subjects will have a lower endoscopy (flexible sigmoidoscopy or colonoscopy) at Visit 
12/Early Termination +/- 3 days to evaluate endoscopic disease activity. Subjects will be 
on a clear liquid diet the day before the lower endoscopy (flexible sigmoidoscopy or 
colonoscopy). On the day of the procedure, the subject will self-administer a bowel prep 
per the PI instructions (e.g., 2 Fleets enemas) and fast for 6 hours before the procedure.   
All subjects will have an in-clinic visit at Visit 12/Early Termination +/- 3 days. 
 
Subjects will then enter the Short Term Safety Follow-up Period in which subjects will 
be contacted by phone on Days 71, 78, 85 +/- 2 days. Subjects will be asked about 
adverse events (AEs), concomitant medications and will complete disease activity 
assessment which includes stool frequency and rectal bleeding, two subscores from the 
total modified Mayo score.  All subjects will have an in-clinic safety visit at Visit 13 +/- 
2 days.  
 
Subjects will then enter the Long Term Safety Follow-up Period in which subjects will 
be contacted by phone on Days 246 +/- 3 days. Following Visit 13 through Day 246/ET 
only SAEs and concomitant medications associated with SAEs will be collected. 
 
To ensure safe study conduct during the Phase 1b study, an independent, unblinded, 
external Data and Safety Monitoring Committee (DSMC) will be established to perform 
safety evaluations on an ongoing basis. A DSMC charter will be developed and will 
detail the review of the safety data.  
3.2!
Criteria for Evaluation of the Study 
The evaluation of the safety data will be performed by comparison of the safety 
endpoints across the treatment arms.  The following safety endpoints will be assessed for 
the comparison: 
•! Incidence of adverse events 
•! Incidence of adverse events of special interest 
•! Laboratory evaluation results 
•! Vital sign measurements 
•! Physical examination findings 
 

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The evaluation of the efficacy data will be performed by comparison of the efficacy 
endpoints across the treatment arms.  The following efficacy endpoints will be assessed 
across treatment arms at various time points between Visit 1 and Visit 13: 
•! Composition of the intestinal microbiome  
•! Engraftment of SER-287 bacteria in all treatment arms 
•! Clinical response defined as:  
o! A decrease of ≥3 points in Total modified Mayo score (TMMS) from 
baseline, along with EITHER a decrease of >1 point in rectal bleeding 
subscore or absolute rectal bleeding subscore of 0 or 1 
•! Complete remission defined as: 
o! A Total modified Mayo score <2 and an endoscopic subscore 0 with no 
erythema, no blood and no evidence of inflammation  
•! Endoscopic improvement, defined as a decrease in endoscopic subscore > 1 
•! Serum biomarker [C-reactive protein (CRP)]  
•! Fecal biomarker (fecal calprotectin) levels 
 
The following exploratory endpoints may also be evaluated across the treatment arms at 
various time points between Visit 1 and Visit 13: 
•! Stool, and blood metabolic pathways 
•! Serum cytokine profile 
•! Mucosal microbiome  
•! Mucosal transcriptomic profile  
•! Mucosal Histopathology, including CMV Immunohistology stains  
•! Microbial Culture Endpoints: 
o! Candida titer and diversity 
 

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4!
STUDY POPULATION 
The study population will consist of adult !18 years of age with mild-to-moderate 
ulcerative colitis. Subjects must be able to provide written consent and meet all the 
inclusion criteria and none of the exclusion criteria. 
4.1!
Inclusion Criteria 
To be eligible for enrollment, a subject must meet all of the following criteria before 
undergoing any study-related procedures: 
1.! Signed informed consent 
2.! Male or female ≥18 years of age 
3.! Ulcerative colitis diagnosed by routine clinical, radiographic, endoscopic and 
pathologic criteria (preferably confirmed by colonoscopy and pathology records 
within last 2 years or if unavailable, will need approval by medical monitor)  
4.! Active mild-moderate UC as determined by lower endoscopy (flexible 
sigmoidoscopy or colonoscopy) within approximately 3 days of randomization to 
study 
a.! Total Modified Mayo score of 4 to 10, inclusive  
b.! Modified Mayo endoscopic subscore of > 1, with evidence of mucosal 
lesions 
c.! At least 15 cm of disease from anal verge 
5.! If female, subject is non-lactating, and is either:  
a.! Not of childbearing potential, defined as postmenopausal for at least 1 
year or surgically sterile due to bilateral tubal ligation, bilateral 
oophorectomy, or hysterectomy  
b.! Of childbearing potential and is practicing at least 1 highly effective 
method of birth control including the barrier method; oral or parenteral 
contraceptives; a vasectomized partner; or abstinence from sexual 
intercourse. The investigator will discuss with the subject the option of 
practicing more than 1 of the above methods for the duration of the study  
6.! If male and partner is of childbearing potential, subject agrees to practice at least 
one highly effective method of birth control for the duration of the study  
4.2!
Exclusion Criteria 
A subject will not be enrolled if the subject meets any of the following criteria: 
1.! Fever > 38.3°C 
2.! Known or suspected toxic megacolon and/or known small bowel ileus 
3.! Known history of Crohn’s disease 
4.! Subjects with serum albumin <2.5 g/dL at baseline 
5.! CMV polymerase chain reaction (PCR) positive from blood plasma at screening 
6.! Known stool tests positive for ova and/or parasites or stool culture within the 
30 days before enrollment 
7.! Subjects on cyclosporine or triple immunosuppression, Triple 
immunosuppression will include any three of the following classes of drugs taken 
in combination: steroids (i.e., prednisone/budesonide/budesonide MMX#), 

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immunosuppressant (i.e., methotrexate/azathioprine/6-mercaptopurine), and/or 
other immunosuppressant (i.e., tacrolimus, cellcept). 
8.! Biologic medication (infliximab/ adalimumab/ golimumab/ 
certolizumab/vedolizumab/ustekinumab/natalizumab) use within 3 months prior 
to screening 
9.! Known active malignancy except for basal cell skin cancer, squamous cell skin 
cancer  
10.!Subjects with previous colectomy, ostomy, J-pouch, or previous intestinal surgery 
(excluding cholecystectomy, appendectomy) 
11.!Subjects with known history of celiac disease or gluten enteropathy 
12.!Subjects with Clostridium difficile positive stool performed by the Central lab at 
Screening Visit  
13.!Antibiotic use within the prior 1 month before randomization  
14.!Expected to receive antibiotics within 8 weeks of signing the Informed Consent 
Form (ICF) (i.e., for planned/anticipated procedure)  
15.!Received an investigational drug within 1 month before study entry 
16.!Received an investigational antibody or vaccine within 3 months before study 
entry 
17.!Previously enrolled in a SER-109/SER-287 study 
18.!Received an FMT within the last 6 months 
19.!Poor concurrent medical risks with clinically significant co-morbid disease such 
that, in the opinion of the investigator, the subject should not be enrolled 
including: 
a.! Subjects with decompensated liver cirrhosis (Child-Pugh Class B or C) or 
uncontrolled liver disease 
b.! Prior history of bone marrow transplant  
c.! Known Hypogammaglobulinemia  
d.! Known severe immunodeficiency 
e.! Underlying liver function test (LFT) [screening alanine aminotransferase 
(ALT) or aspartate aminotransferase (AST)] abnormalities greater than 2x 
upper limit of normal (ULN) 
f.! Absolute neutrophil count (ANC) <500 
20.!Subjects with anatomic or medical contraindications to lower endoscopy (flexible 
sigmoidoscopy or colonoscopy), including but not necessarily limited to toxic 
megacolon, gastrointestinal (GI) fistulas, immediate post-operative status from 
abdominal surgery, severe coagulopathy, large or symptomatic abdominal aortic 
aneurysm, or any subject where study physician deems subject at significant risk 
of complications of lower endoscopy (flexible sigmoidoscopy or colonoscopy) 
21.!Unable to stop steroid enemas or suppositories or mesalamine enemas or 
suppositories before screening visit 
22.!Unable to stop opiate treatment unless on a stable dose and no increase in dose 
planned for the duration of the study 
23.!Unable to stop probiotics before screening visit 
24.!Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment 
for active malignancy (subjects on maintenance chemotherapy may only be 
enrolled after consultation with medical monitor) 

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25.!Unable to comply with the protocol requirements  
26.!Any condition that, in the opinion of the investigator, might interfere with study 
objectives 
27.!Known allergy or intolerance to oral vancomycin 
28.!Known active intravenous drug or alcohol abuse or use of other drugs of abuse 
4.3!
Subject Withdrawal and Replacement 
Subjects should continue to be followed for safety assessments through 24 weeks after 
treatment, even after being discontinued from study medication.  However, a patient may 
withdraw from the study at any time for any reason, without any consequence.  
 
Subjects may be required to withdraw from study after discussion with the Sponsor and/or 
Investigator for the following reasons: 
•! Pregnancy (see Section 6.2.2.4); 
•! Adverse event(s); 
•! Met at least one of the safety halting rules (see Section 6.2.2.1) 
•! At the discretion of the Investigator 
•! Protocol violation 
•! Non-compliance 
 
In all cases, the reason(s) for withdrawal will be recorded on the electronic data capture 
(EDC) system. If a subject is prematurely withdrawn from the study drug for any reason 
before Visit 12, the Investigator must make every effort to perform the evaluations 
described for Follow Up Visit 12. 
If a subject withdraws consent and still agrees to undergo a final examination, this will 
be documented on the EDC system and the Investigator’s copy of the ICF, which will be 
countersigned and dated by the subject.  
A subject may also be withdrawn from study by the Sponsor, Regulatory Authorities, or 
Independent Ethics Committees (IECs)/Institutional Review Boards (IRBs). 
Subjects will also be withdrawn if the entire study is terminated prematurely. 
If a subject fails to appear for a follow-up assessment, all attempts to contact the subject 
and information received during contact attempts must be documented in the subject’s 
medical record. In any circumstance, every effort should be made to document subject 
outcome, if possible (i.e, 3 documented contact attempts via phone calls, e-mail, etc., on 
separate occasions will be made to locate or contact them, or at least to determine their 
health status). 
Subjects who discontinue from the study after randomization may be replaced.  
4.4!
Planned Sample Size and Number of Study Centers 
Approximately 55 subjects will be enrolled at approximately 20 sites in the United States 
(US).  

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4.5!
Subject Identification and Randomization 
4.5.1! Subject Identification 
All screened subjects will be assigned a unique subject identification (SID) number that 
will be used through screening, pre-treatment and treatment periods, and safety follow-up 
period.  
4.5.2! Methods of Assigning Patients to Study Treatment 
Randomization will be used to avoid bias in the assignment of subjects to double-blind 
treatment (SER-287 or placebo) and to increase the likelihood that known and unknown 
subject characteristics will be evenly distributed between the treatment groups.  
Eligible subjects are to be randomized at Visit 3 (Day 1) after all screening procedures 
have been performed and eligibility for the study confirmed. Subjects will be randomized 
via interactive voice/web response system (IxRS) to one of 4 study arms: A) Pre-
treatment of placebo, followed by weekly dosing of SER-287 for 8 weeks; B) Pre-
treatment of placebo, followed by daily dosing of placebo for 8 weeks; C) Pre-treatment 
of vancomycin, followed by daily dosing of SER-287 for 8 weeks; D) Pre-treatment of 
vancomycin, followed by weekly dosing of SER-287 for 8 weeks.  
 
Once a randomization number has been assigned to a subject, the number cannot be 
reused even if the subject discontinues from the study early or withdraws before 
receiving any study drug. Subjects who discontinue from the study or who have been 
previously randomized in the study will not be permitted to re-enter. Similarly, study 
drug assigned to a subject may not be re-used, even if the bottle is returned unopened.  
During the double-blind period, subjects, the investigators and other study site personnel, 
and clinical staff will remain blinded to the treatment assignment. The medical monitor, 
study site monitors, and other sponsor representatives involved in the clinical aspects of 
study conduct also will remain blinded to the treatment assignment.  
4.5.3! Maintaining the Randomization Codes and Breaking the Study Blind 
A designated randomization administrator from an external, independent vendor will 
maintain the randomization codes in accordance with standard operating procedures to 
ensure that the blind is properly maintained and that only sponsor personnel who require 
knowledge of treatment assignments will be unblinded [e.g., staff involved in serious 
adverse event (SAE) reporting].  
Investigators are not to break the study treatment blind except when information 
concerning the study drug is necessary for the medical treatment of the subject. If a 
medical emergency requiring unblinding occurs, the investigator (or designated 
physician) is strongly encouraged to contact the medical or safety monitor to assess the 
necessity of breaking the study drug blind. If unblinding is warranted, the investigator 
will obtain the treatment assignment information from the IxRS. Every effort is to be 
made to limit study site personnel unblinding only to those individuals providing direct 
care to that subject. Any intentional or unintentional breaking of the blind is to be 
reported immediately to the sponsor. The other circumstances in which unblinding may 
be necessary are at the request of a subject who becomes pregnant during the study or for 

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regulatory reporting purposes.  
 
If the blind is broken, the date, time, and reason must be recorded in the patient’s EDC 
system, and any associated AE report.  
 
If a subject is unblinded, they will not receive any additional study medications. 
After the statistical analysis plan (SAP) is final and the primary study period (Visit 1 
through Visit 13) data is declared complete and final, the study blind codes will be 
broken. 
 

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5!
INVESTIGATIONAL PRODUCT 
5.1!
SER-287 
5.1.1! Donor Screening 
Donors undergo a general health examination including GI medical history, familial GI 
medical history, clinical chemistry, hematology with complete blood count, urinalysis, 
and blood and fecal viral and bacterial pathogen testing before donating stool. The donor 
must successfully complete the physical screening and laboratory tests after the donation 
period before the material can be released for manufacturing. A description of donor 
screening procedures is provided in the Investigator’s Brochure.  
5.1.2! SER-287 Manufacturing 
SER-287 is manufactured as SER-109 using current Good Manufacturing Practice -
compliant processing steps, and is subsequently released using assays for purity, potency, 
and identity. The manufacturing process inactivates non-spore forms of bacteria, fungi, 
and other potential components (parasites and some viruses), substantially reduces the 
amount of undigested food and inactivated vegetative biomass via successive filtration 
steps, and formulates the drug substance in 92% glycerol and approximately 8% saline 
solution (0.9% of sodium chloride), containing less than about 30 mg of non-spore 
solids.  The drug substance is filled into capsules, and then over-encapsulated. For each 
unit-dose bottle, four capsules (1×108 SporQs) are packaged in an HDPE container, 
induction sealed with foil and closed with child resistant closures. At the time of labeling 
for investigational use the drug product becomes SER-287. SER-287 is odorless and 
tasteless as prescribed. If chewed or if capsule integrity is compromised, SER-287 has a 
sweet taste. 
Study drug will be packaged by Catalent Pharma Solutions according to all local legal 
requirements. Study drug will be labeled in accordance with applicable regulatory 
requirements. 
5.2!
Over-encapsulated (OE) Vancomycin HCl 125 mg Capsules, Hard Gelatin 
Capsules (“Vancomycin”) 
5.2.1! Vancomycin HCl Procurement, Over-encapsulation, Packaging and Storage 
Commercially available Vancomycin HCl 125 mg Capsules, USP, in 20-capsule blister 
packs are de-blistered and over encapsulated in size 00 Swedish Orange Capsules with 
microcrystalline cellulose backfill.  Capsules are filled into 40 mL white high density 
polyethylene (HDPE) bottles, induction sealed with a foil seal and closed with child 
resistant closures.  Each bottle is filled with 24 capsules.  Bottles are stored at ambient 
temperature.     

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5.3!
SER-287 Placebo Capsules 
5.3.1! SER-287 Placebo Manufacturing 
Placebo will be identical to the Investigational Product SER-287 but will not contain 
product spores or non-spore solids. Placebo will consist of 92% glycerol and 
approximately 8% saline solution (0.9% of sodium chloride).  The SER-287 Placebo will 
be provided in a single-dose container of 4 white, size 00 capsules in a foil-sealed, 
opaque, 40 mL HDPE bottle with child resistant closures. At the time of labeling for 
investigational use the placebo becomes SER-287 placebo.  The SER-287 placebo is 
odorless and tasteless as prescribed. If chewed or if capsule integrity is compromised, 
SER-287 placebo has a sweet taste. 
5.4!
Vancomycin HCl Placebo Capsules (“Vancomycin Placebo”) 
5.4.1! Vancomycin HCl Placebo Manufacturing and Storage 
Vancomycin HCl placebo is manufactured in size 00 Swedish Orange Capsules.  
Capsules are filled with microcrystalline cellulose and filled into 40 mL white HDPE 
bottles.  Bottles are induction sealed with a foil seal and closed with child resistant 
closures.  Each bottle is filled with 24 capsules.  Bottles are stored at ambient 
temperature. 
5.5!
Storage 
5.5.1! SER-287 and SER-287 Placebo Storage 
SER-287 or placebo bottles are assembled into weekly kits and stored at or below -15°C 
at the distribution depot. Kits are shipped to the clinical site on dry ice.  Kits are stored at 
or below -15°C at the clinical site until dispensed to the subject.  Subjects are instructed 
to store kits at home in the refrigerator (2°C-8°C).  For more information on storage, 
refer to the Study Manual. 
The doses, route, and schedule of study drug administration are shown in Table 1, below:  
 
 
 
 
 
 
 
 

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Table 1: Doses, Route, and Schedule of Study Drug Administration 
Group 
Pre-treatment: Vanco or Pbo 
  Treatment Period:  SER-287 or Pbo 
Vanco 
or Pbo 
Regimen 
Admin 
Duration 
  
SER-287 
or Pbo 
Regimen 
Admin 
Duration 
A 
Pbo 
Pbo 
One 
capsule 
four 
times 
daily 
orally 
6 days 
  
SER-287 
+ Pbo 
SER-287 
Weekly 
(1x108 
SporQs) 
+Pbo 
6d/wk 
Four 
capsules 
once daily 
orally 
8 wks 
B 
Pbo 
Pbo 
One 
capsule 
four 
times 
daily 
orally  
6 days 
  
Pbo 
Placebo 
Daily 
Four 
capsules 
once daily 
orally 
8 wks  
C 
Vanco 
Vanco 
125 mg 
qid 
One 
capsule 
four 
times 
daily 
orally 
6 days 
  
SER-287  
SER-287 
Daily 
(1x108 
SporQs)   
Four 
capsules 
once daily 
orally 
8 wks 
D 
Vanco 
Vanco 
125 mg 
qid 
One 
capsule 
four 
times 
daily 
orally 
6 days 
  
SER-287 
+ Pbo 
SER-287 
Weekly 
(1x108 
SporQs) 
+Pbo 
6d/wk   
Four 
capsules 
once daily 
orally 
8 wks 
d = day; Pbo = placebo; qid = Four times a day; wk = week; admin= administration;  
vanco=vancomycin; SporQs= spore equivalents 
 
After the primary study period (Visit 1 to Visit 13) data is declared complete and final, the 
overall randomization code will be broken only for reporting purposes. The record of 
randomization will include study arm assignment and also the association of treatment kit 
number with donor group.  
5.6!
Drug Accountability 
The Investigator is responsible for maintaining accurate study drug accountability 
records throughout the study. 
 
Vancomycin or Vancomycin placebo are provided in sealed bottles containing 24 
capsules.  The seal on a given bottle should be punctured at the time of subject 
randomization to perform drug accountability at the capsule level. Each bottle should be 
stored unopened and intact until dispensed to the subject.  
 
SER-287 or SER-287 placebo are provided in sealed bottles containing four capsules. 
The seal on a given bottle should only be removed at the time of administration. Each 
bottle should be stored unopened and intact until time-of-use. Drug accountability at the 

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clinical site should be done both at the kit level and at the individual unit-dose bottle 
level.  
5.7!
Prior and Concomitant Medications 
Any medication the subject takes through Visit 13 other than the study drug (vancomycin 
and SER-287), including herbal and other non-traditional remedies, is considered a 
concomitant medication.  Following Visit 13 through Day 246/ET only concomitant 
medications associated with SAEs will be collected.  All concomitant medications must 
be recorded in the EDC system. The following information must be recorded in the EDC 
system for each concomitant medication: generic name (or trade name if generic is not 
known), route of administration, start date, stop date, dosage, and indication. Any 
changes in the dosage or regimen of a concomitant medication must be recorded in the 
EDC system. 
 
At Screening, subjects will be asked about all current and prior IBD medications they 
have taken and in addition all medications taken during the last 6 months (non-IBD 
related)  At each subsequent study visit, subjects will be asked what concomitant 
medications they are currently taking. 
 
Permitted concomitant medications include: 
•! Oral aminosalicylates (Aminosalicylates taken for at least 6 weeks, with a stable 
dose for > 2 weeks prior to screening)  
•! Immunomodulator: 6-Mercaptopurine, Azathioprine, Methotrexate (Stable dose 
for > 12 weeks prior to screening) 
•! Prednisone < 15 mg (Stable dose for > 2 weeks prior to screening) 
•! Budesonide < 6 mg (Stable dose for > 2 weeks prior to screening 
•! Budesonide MMX# < 9 mg (Stable dose for > 2 weeks prior to screening) 
•! Opiate treatment (stable dose) 
•! Short term opiate use is permitted 
•! Short term use of non-steroidals/NSAIDS, is permitted 
•! Low dose aspirin (81mg) is permitted for long-term use 
 
Subjects who are receiving any of the above permitted concomitant medications at the 
time of study entry must keep their dosage stable throughout the study, unless 
investigator judgment requires it to be increased, reduced or discontinued for safety 
concerns or medical necessity.  If there is a change in dosage, the subject would then be 
discontinued from the study.   
 
 
 
 
 

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The following prohibited concomitant medications may not be administered at any 
time through the study period.  Subjects who initiate the following treatments will be 
discontinued from further study agent administration. 
•! Probiotics  
•! Loperamide, diphenoxylate/atropine, or bile-salt sequestrant (cholestyramine, 
colesevelam) 
•! Cyclosporine or triple immunosuppression 
•! Biologic medication (infliximab/ adalimumab/ golimumab/ certolizumab/ 
vedolizumab/ ustekinumab/ natalizumab) 
 

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6!
VARIABLES AND METHODS OF ASSESSMENT 
6.1!
Microbiome Alterations and Engraftment Primary Endpoints 
6.1.1! Microbiome Alterations 
Stool samples will be analyzed to characterize changes in the microbiome and associated 
functional metabolic changes in the gastrointestinal tract at various time points between 
Visit 1 and Visit 13.  
 
Composition of the intestinal microbiome 
Composition of the intestinal microbiome will be assessed at time points between Visit 1 
and Visit 13. 
 
Engraftment of SER-287 bacteria 
Engraftment is defined as the outgrowth of bacteria that comprise the SER-287 spore 
ecology in a subject’s gastrointestinal tract post-treatment. Engraftment of SER-287 
bacteria will be assessed at time points between Visit 4 and 13. 
  
Secondary Endpoints 
6.1.2! Clinical Response, Complete Remission, and Endoscopic Improvement 
Partial Mayo score, which is the Mayo Score without the endoscopic subscore, will be 
assessed at each visit and the Total modified Mayo score (TMMS) will be assessed at 
baseline and at Visit 12 (or early termination) 
Clinical response is defined as:  
$! A decrease of ≥3 points in TMMS from baseline, along with EITHER a decrease 
of >1 point in rectal bleeding subscore OR absolute rectal bleeding subscore of 0 
or 1 
Complete remission is defined as: 
$! A TMMS <2 and an endoscopic subscore of 0 with no erythema, no blood and no 
evidence of inflammation  
Endoscopic improvement is defined as: 
$! a decrease in the modified Mayo endoscopic subscore > 1  
6.1.3! Biomarkers 
The following biomarkers will be evaluated at time points between Visit 1 and Visit 13.  
•! Serum biomarkers (CRP)  
•! Fecal biomarkers (fecal calprotectin) levels  
 
 
 

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6.1.4 Exploratory Endpoints 
The following exploratory endpoints may be evaluated. Please refer to schedule of 
assessments for times collected.  
•! Stool and blood metabolic pathways  
•! Serum cytokine profile 
•! Mucosal transcriptomic profile  
•! Mucosal microbiome  
•! Mucosal Histopathology, including CMV Immunohistology stains  
•! Microbial Culture Endpoints: 
o! Candida titer and diversity 
6.2!
Safety Variables 
Safety evaluations include medical history, assessment of AEs, clinical laboratory tests 
(chemistry, hematology and urinalysis), physical examination, vital signs, and 
electrocardiograms (ECGs).  
6.2.1! The Safety Endpoints 
•! Incidence of adverse events 
•! Incidence of adverse events of special interest 
•! Laboratory evaluation results 
•! Vital sign measurements 
•! Physical examination findings 
6.2.2! Adverse Events 
An adverse event (AE) is defined as any untoward medical occurrence in a subject who 
was administered study drug, regardless of its causal relationship to the study drug. An 
AE can, therefore, be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of the study 
drug, whether or not it is considered to be related to the study drug. 
 
A serious adverse event (SAE) is any AE occurring at any dose and regardless of 
causality that: 
•! Results in death. 
•! Is life-threatening. Life-threatening means that the subject was at immediate risk of 
death from the reaction as it occurred, i.e., it does not include a reaction that 
hypothetically might have caused death had it occurred in a more severe form. 
•! Requires in-patient hospitalization or prolongation of existing hospitalization; 
hospital admissions and/or surgical operations scheduled to occur during the study 
period, but planned before study entry are not considered AEs if the illness or disease 
existed before the subject was enrolled in the study, provided that it did not worsen in 
any unexpected manner during the study (e.g., surgery performed earlier than 
planned). 

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Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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•! Results in persistent or significant disability/incapacity. Disability is defined as a 
substantial disruption of a subject’s ability to conduct normal life functions. 
•! Is associated with a congenital anomaly/birth defect. 
•! Is an important medical event. An important medical event is an event that may not 
result in death, be life-threatening, or require hospitalization but may be considered 
an SAE when, based upon appropriate medical judgment, it may jeopardize the 
subject and may require medical or surgical intervention to prevent 1 of the outcomes 
listed in the definitions for SAEs. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias, convulsions that do not result in in-patient hospitalization, and the 
development of drug dependency or drug abuse. 
 
An adverse event of special interest (AESI) (serious or non-serious) is one of scientific 
and medical concern specific to the product or program, for which ongoing monitoring 
and rapid communication by the investigator to the sponsor is appropriate. 
 
In this protocol, a UC flare, as defined in Section 6.2.2.1 below, has been designated as 
an AESI and as such will be reported and followed in the same manner as a SAE during 
the course of the study.    
 
All AEs, including SAEs, will be graded for severity by using the following grading 
system: 
•! Mild: Events require minimal or no treatment and do not interfere with the subject’s 
daily activities 
•! Moderate: Events result in a low level of inconvenience or concern and may require 
treatment; moderate events may cause some interference with functioning 
•! Severe: Events interrupt a subject’s usual daily activity and may require systemic 
drug therapy or other treatment; severe events are usually incapacitating 
 
Changes in the severity of an AE will be documented, and documentation will include 
assessment of the duration of the event at each level of intensity. Adverse events 
characterized as intermittent will be documented based on the severity, onset, and 
duration of each episode. 
An abnormal laboratory test finding that meets any of the criteria below will be 
considered an AE: 
•! Is associated with accompanying symptoms 
•! Requires additional diagnostic testing or medical/surgical intervention 
•! Leads to a concomitant drug treatment or any change in a concomitant medication or 
therapy 
•! Is considered an AE by the Investigator 
Laboratory results that fall outside the reference range and do not meet 1 of the criteria 
above will not be reported as AEs. Repeating a test because of an abnormal result, in the 

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Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  41 of 75                                                  10 Oct 2016  
absence of the above conditions, does not constitute as AE. Any abnormal test result that 
is determined to be an error will not be reported as an AE. 
For all AEs, including SAEs, the Investigator will report on the relationship of the AE to 
the study drug by using the following definitions: 
•! Unrelated: There is little or no chance that the study drug caused the AE; other 
conditions, including concurrent illnesses, progression or expression of the disease 
state, or a reaction to a concomitant medication best explain the event 
•! Related or Possibly Related: The association of the AE with the study drug is 
unknown; however, the AE is not clearly due to another condition, or a reasonable 
temporal association exists between the AE and treatment administration and, based 
on the Investigator’s clinical experience, the association of the AE with the study 
drug seems likely 
Adverse events, including local and systemic reactions not considered medically serious, 
will be recorded. Information to be collected includes event description, time of onset, 
Investigator assessment of severity, relationship to study drug, date of resolution of the 
event, seriousness, and outcome. 
Any medical condition that is present at the time that the subject is screened will be 
considered as a baseline condition and not be reported as an AE. However, if it worsens 
at any time during the study, it should be recorded as an AE. 
 
All AEs, SAEs and AESIs will be collected from Informed Consent up to Visit 13.  
Following Visit 13 through Day 246, only SAEs will be collected.  All AEs, including 
SAEs and AESIs, will be monitored until resolution or determined by the Investigator to 
be due to a subject’s stable or chronic condition or intercurrent illness. 
The Investigator is responsible for: 
•! Informing the sponsor in the event that a patient or a subject’s partner becomes 
pregnant during the study. A “Pregnancy Report Form” will be generated and the 
pregnancy will be captured in the safety database and will be followed through to the 
outcome. 
•! Evaluating subject safety including assessment of AEs for seriousness, severity, and 
causality. 
Informing the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) of 
AEs as required and SAEs as per IRB/IEC guidelines. 
6.2.2.1! Safety Halting Rules 
 
To ensure subject safety, individual (as listed below) and study-wide (as detailed in the 
DSMC charter) halting rules will be implemented. 
 
Individual halting rules include: 
•! UC flare, defined by: 1) an increase by 2 points from screening of partial Mayo score 
at two contiguous visits after SER-287/placebo initiation (if the partial Mayo score 
changes from Visit 1 to Visit 2, the Visit 2 score should be used in computing the 

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Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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partial Mayo score at Baseline for the individual halting rules), AND 2) worsening 
clinical status warranting change in UC treatment as determined by principal 
investigator. 
•! Any SAE that is serious, related to study drug, and unexpected, which when referred 
to the DSMC the recommendation is to withdraw the subject from the study. 
If a subject meets the criteria above for at least one of the individual halting rules, he/ she 
will be discontinued from the study. 
6.2.2.2! Reporting Serious Adverse Events 
The Investigator must report any SAEs and AESIs to the PAREXEL Medical Services 
Safety Contact within 24 hours of becoming aware of the event by completing and 
transmitting the Serious Adverse Event report form by fax or email to the PAREXEL 
Safety Contact noted below. If questions arise regarding the reporting procedures or the 
specifics of the reporting event or the site needs to report the event by phone, the 
investigator may call the Safety Contact listed below. A phone report will need to be 
followed by faxing or emailing the written SAE report form within the next 24 hours.  
 
The Sponsor (or Sponsor’s designated agent) will review each SAE report in detail and 
will evaluate the expectedness according to the reference document (Investigator 
Brochure or Summary of Product Characteristics). Based on the Investigator and 
Sponsor’s assessment of the event, a decision will be made concerning the need for 
expedited reporting to regulatory authorities. 
SERIOUS ADVERSE EVENT/ADVERSE EVENTS OF SPECIAL INTEREST 
REPORTING INSTRUCTIONS 
PAREXEL International Corporation 
North America Medical Services 
Telephone Number: +1-781-434-5010 
Fax Number: +1-781-434-5957 
 
Email: NorthAmerica_Medical@PAREXEL.com 
Fax the SAE/AESI report form and any supporting documentation to the PAREXEL 
Medical Services Safety Team within 24 hours of becoming aware of the event. 
The SAE/AESI report form should be completed in its entirety as much as possible. If 
only a partial SAE report is available, preliminary information will be documented on the 
SAE/AESI Report Form and transmitted to the PAREXEL Safety contact within 24 
hours of site awareness. The minimum information required for an initial report is: 
•! Name of person sending the report (i.e., name, address of Investigator); 
•! Subject identification (screening/randomization number, initials, NOT subject name); 
•! Protocol number; 
•! Description of SAE/AESI; 
•! Causality assessment, if possible. 

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Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  43 of 75                                                  10 Oct 2016  
When additional relevant information is available, the SAE/AESI report form will be 
updated with the new information and submitted within 24 hours of site awareness of this 
new information. The event must be documented in the eCRF. 
6.2.2.3! Follow-up of Adverse Events 
All AEs experienced by a subject, irrespective of the suspected causality, will be 
monitored until the AE has resolved, any abnormal laboratory values have returned to 
baseline or stabilized at a level acceptable to the Investigator and Medical Monitor, until 
there is a satisfactory explanation for the changes observed, until the subject is lost to 
follow-up, until it is unlikely that any additional information can be obtained, or until the 
subject has died. 
6.2.2.4! Pregnancy 
The Sponsor has a responsibility to monitor the outcome of pregnancies where there has 
been maternal exposure to the study drug.  
Pregnancy alone is not regarded as an AE unless there is a suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication. 
Elective abortions without complications should not be handled as AEs, unless they were 
therapeutic abortions (see below). Hospitalization for normal delivery of a healthy 
newborn should not be considered a SAE. 
All pregnancies must be reported by the Investigator to PAREXEL/Sponsor on the initial 
pregnancy report form within 24 hours after becoming aware of the pregnancy. The 
Investigator must follow up and document the course and the outcome of all pregnancies 
even if the subject was discontinued from the study or if the study has finished. 
All outcomes of pregnancy must be reported by the Investigator to PAREXEL/Sponsor 
on the pregnancy outcome report form within 24 hours after he or she has gained 
knowledge of the normal delivery or elective abortion. 
Any SAE that occurs during pregnancy (including SAEs occurring after last 
administration of study drug) must be recorded on the SAE report form (e.g., maternal 
serious complications, spontaneous or therapeutic abortion, ectopic pregnancy, stillbirth, 
neonatal death, congenital anomaly, or birth defect) and reported within 24 hours in 
accordance with the procedure for reporting SAEs 
If a female partner of a male study subject who has been exposed to the study drug 
becomes pregnant, the pregnancy and outcome of pregnancy should be monitored. 
In the event of pregnancy, the pregnancy should be followed until the outcome of the 
pregnancy is determined. 
6.2.3! Laboratory Variables 
Laboratory assessments will be performed by a central laboratory, as identified in the 
List of Study Personnel. 
Blood samples will be taken using standard venipuncture techniques. A laboratory 
manual will be provided by the central laboratory. This laboratory manual will contain 
detailed instructions for collection, storage, and shipment of samples (e.g., what kind of 
tubes, what kind of sample preparation, mailing addresses, etc.).   

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Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  44 of 75                                                  10 Oct 2016  
The following laboratory variables (Table 2) will be determined in accordance with the 
Schedule of Events (Table 3).  
 
Table 2: Laboratory Assessments 
Hematology: 
erythrocytes 
mean corpuscular volume (MCV) 
mean corpuscular hemoglobin (MCH) 
neutrophils 
eosinophils 
basophils 
lymphocytes 
monocytes 
platelets 
leukocytes 
hemoglobin 
hematocrit 
Urinalysis1: pH 
protein 
glucose 
ketone 
bilirubin 
blood 
nitrite 
leukocyte esterase 
Clinical 
chemistry: 
creatinine 
glucose 
triglycerides 
urea 
uric acid 
cholesterol 
albumin 
Liver 
enzymes: 
ALP 
AST 
ALT 
GGT 
direct and indirect 
bilirubin 
total bilirubin 
Electrolytes: 
sodium 
potassium 
 
 
Pregnancy test2: In women with childbearing potential only 
ALP = alkaline phosphatase; ALT =  alanine aminotransaminase; AST = aspartate aminotransferase; CBC = 
complete blood count; GGT = γ-glutamyl transferase; RBC =  red blood cells; WBC = white blood cells. 
1 Urinalysis will be performed by dipstick.  If nitrates or leukocytes are positive, a microscopic 
examination will be performed by the central laboratory. 
2 A serum pregnancy test will be done at Screening.  Urine pregnancy tests will be done at Visit 3 (Day 1), 
Visit 12 (Day 64 ± 3) and at Visit 13 (Day 92 ± 1).  
 
Any value outside the normal range will be flagged for the attention of the Investigator or 
designee at the site.  The Investigator or designee will indicate whether or not the value is 
of clinical significance and should be recorded as an AE.  Actual laboratory results will 
not be captured on the EDC system. However, if any laboratory results meeting the 
reporting requirements for an AE, the event term (e.g., elevated transaminase) will be 
recorded on the EDC system as an AE or SAE, as applicable. 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  45 of 75                                                  10 Oct 2016  
6.2.4! Stool Samples 
Stool samples will be collected by the subjects and brought to the clinic at Visit 1, Visit 
4, Day 11, Visit 5, Day 18, Visit 6, Visit 12 and Visit 13 or the Early Termination Visit 
(if applicable), and any Unscheduled Visit. 
6.2.5! Biopsy Samples  
A total of 4 biopsies will be obtained between 15 and 30 cm of the colon both at Visit 2 
and at Visit 12.  One biopsy sample will be placed in formalin and 3 biopsies will be 
placed in RNALater.  At the clinical site, samples will be processed and then shipped to 
the central laboratory according to procedures defined in the Laboratory Manual.   
6.2.6 Vital Signs 
The following vital signs will be assessed in accordance with the Schedule of Events 
(Table 2): 
•! Blood pressure (BP; systolic and diastolic; mmHg); 
•! Heart rate (HR; beats per minute); 
•! Oral body temperature (°C); 
•! Respiration rate (breaths per minute). 
•! Height (taken at Screening only) 
•! Weight 
The Investigator or designee will indicate whether or not a value is of clinical 
significance and should be recorded as an AE.   
6.2.7! Electrocardiograms 
Standard 12-lead ECGs will be performed in accordance with the Schedule of Events 
(Table 2). 
Standard safety 12-lead ECGs (single reading) will be performed at Day 8 (before 
dosing), and at Follow-Up on Day 92 as shown in Table 2, the Schedule of Events. 
All ECGs will be evaluated by a qualified physician or delegate for the presence of 
abnormalities.  The Investigator or designee will indicate whether or not a value is of 
clinical significance and should be recorded as an AE.  The ECG data will be collected 
as: Normal; Abnormal, Not Clinically Significant; and Abnormal, Clinically Significant.  
6.2.8! Physical Examinations 
Physical examinations will be performed in accordance with the Schedule of Events 
(Table 2).   
The physical examination includes an assessment of general appearance and evaluation 
of the following: Head/Eyes/Ears/Nose/Throat; Neck; Lungs and Heart; Abdomen; 
Extremities; Neurological; Other. 
Abnormal clinically significant findings will be reported as medical history or AEs as 
determined by Investigator. 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  46 of 75                                                  10 Oct 2016  
6.3!
Demographics and Baseline Characteristics 
Demographics and Baseline Characteristics consist of those variables that are assessed 
only at screening/baseline. 
6.3.1! Subject Demography 
•! Age at screening; 
•! Sex; 
•! Height; 
•! Weight; 
•! Ethnic origin (Hispanic/Latino or not Hispanic/not Latino); 
•! Race (White, American Indian/Alaska Native, Asian, Native Hawaiian or other 
Pacific Islander, Black/African American). 
6.3.2! Disease History 
For disease history the following will be documented: 
•! Date of first diagnosis; 
•! Montreal classification 
6.3.3! Baseline Characteristics 
•! General medical history 
•! General surgical history 
•! Smoking history 
6.3.4! Medical History 
For the documentation of the medical history, any previous and concomitant diseases 
before screening will be documented. The medical history will be obtained by 
interviewing the subject or by inspecting his/her medical records. 
6.3.5! Prior and Concomitant Medications 
Prior and concomitant medication will be documented as described in Section 5.7.  Prior 
and concomitant medications will be coded using the WHO Drug Dictionary. 
 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  47 of 75                                                  10 Oct 2016  
7!
STUDY CONDUCT 
7.1!
Schedule of Events 
The study consists of a Screening Visit (Days -17 to -1), a Screening Visit for lower 
endoscopy (flexible sigmoidoscopy or colonoscopy) (at least 3 days before Day 1), a 
pretreatment period (Days 1 to 7), a treatment period (Days 8 to 63), and Short Term 
Safety Follow-up (Day 64 to 92) and a Long Term Safety Follow-up (Day 93-246).  The 
maximal study duration for an individual subject will be 260 days. 
The Schedule of Events is presented in Table 3.  

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  48 of 75                                                  10 Oct 2016  
Table 3: Schedule of Events 
 
VISIT NAME
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Visit 12/ET (j)
Phone calls
Visit 13
Phone call
Day 11(d)
Day 18(d)
Visit/Phone Call
Pre-Treatment Drug 
Dosing
X (c)
Study Drug Dosing 
X(c)
Informed consent
X
Inclusion/ Exclusion 
Criteria
X
X
Central Reading 
Results
X (o)
X
Medical history
X
Randomization
X
Demographic data
X
Physical Ex
X
X
X
X
X
X
Vital signs (a)
X
X
X
X
X
X
ECG
X (b)
X
Bowel Prep (i)
X
X
Lower Endoscopy
X
X
Overnight Fast 
(required for 
endoscopy; when 
possible for other 
visits)
X (k)
X
X 
X 
X 
X (k)
X 
Blood Testing
Hematology
X (g)
X (b)
X(b)
X
X
Clinical chemistry
X (g)
X(b)
X(b)
X
X
CMV PCR (l)
X (g)
Pregnancy test 
(WOCBP)
X (g)
Blood for biomedical 
research
X (b)
X
Blood for 
metabolomics
X (h)
X (b)
X
X
X
X
Blood for CRP
X
X (b)
X
X
X
X
Serum Cytokine
X (h)
X
Visit
Visit
Visit
Visit
Visit
Phone call
Visit
Phone call
Visit
VISIT DAY
Visit for 
sigmoidoscopy(f
)
Visit
Visit
Stool sample
Visit
Stool sample
Visit
Visit
Screening with  lower 
endoscopy (flexible 
sigmoidoscopy or colonoscopy) 
(Day -17 to Day -1 )
Treatment Period (Day 8-Day 63)
Safety Follow Up Period (Day 64-246) 
Day 8 +/- 1d
Day 1
Day 15 +/-1d
Day 22+/-1d
Day 29 +/-1d
Day 36 +/-1d
Day 43  +/-1d
Day 50 +/-1d
Day 57+/-1d
Day 64+/-3d
Weekly on 
Days 71, 78, 
85+/-2d
Day 92+/-2d
Day 246 +/-3d
Pre-Treatment 
Period (Day 1-7)
 

Seres Therapeutics, Inc 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
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Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  50 of 75                                                  10 Oct 2016  
Table 3: Schedule of Events (continued) 
 
VISIT NAME
Visit 1
Visit 2
Visit 3
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Visit 12/ET (j)
Phone calls
Visit 13
Phone call
Day 246 +/-3d
Day 11(d)
Day 18(d)
Urine Testing
Urine Pregnancy
X
X 
X
Urinalysis (e)
X
X (b)
X
X
Stool Testing
Stool for 
Microbiome
X (h)
X (b)
X
X
X
X
X
Stool for Microbial 
Culture
X (h) 
X (b)
X
X
X
X
 X
Stool for 
Metabolomics
X (h) 
X(b)
X
X
X
X
Stool for cdiff
X (g)
Stool for Fecal 
calprotectin
X (h) 
X (b)
X
X
X
Biopsies
Mucosal 
Transcriptomics (2 
samples)
X
X
Mucosal Microbiome 
(1sample)      
X
X
Histopathology with 
CMV Stain (1 
sample)
X
X
Visit
Visit
Phone call
Visit
Phone call
Visit
Visit
Visit
Visit
X
Screening with  lower endoscopy 
(flexible sigmoidoscopy or 
colonoscopy) (Day -17 to Day -1 )
Pre-Treatment 
Period (Day 1-7)
Treatment Period (Day 8-Day 63)
Safety Follow Up Period (Day 64-246) 
Short Term Safety Follow-up (Day 64 to 92 ) and a Long Term Safety 
Follow-up (Day 93-246). 
Day 64+/-3d
Weekly on 
Days 71, 78, 
85+/-2d
Day 92+/-2d
Visit 4
Visit 5
VISIT DAY
Day 1
Day 8 +/- 1d
Day 15 +/-1d
Day 22+/-1d
Day 29 +/-1d
Day 36 +/-1d
Day 43  +/-1d
Day 50 +/-1d
Day 57+/-1d
Visit/Phone Call
Visit
Visit for  lower 
endoscopy 
(flexible 
sigmoidoscopy 
or 
Visit
Visit
Stool sample
Visit
Stool sample
Visit
X
 
 
 

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Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  51 of 75                                                  10 Oct 2016  
Table 3: Schedule of Events (continued) 
 
VISIT NAME
Visit 1
Visit 2
Visit 3
Visit 6
Visit 7
Visit 8
Visit 9
Visit 10
Visit 11
Visit 12/ET (j)
Phone calls
Visit 13
Phone call
Day 246 +/-3d
Day 11(d)
Day 18(d)
Study Drug 
Dispensation
Dispense pre-trtmt 
drug
X
Return pre-trmt 
drug
X
Dispense study drug 
( q )
X
X
X
X
X
X
X
Return study drug
X
X
X
X
X
X
X
Other
Diet Inventory
X
X
X
X
Partial Mayo score
X
X
X
X
X
X
X
X
X
X
X
X 
X
X
Safety Follow Up Period (Day 64-246) 
X
Visit
X
X
Treatment Period (Day 8-Day 63)
Visit
Visit
Visit
Visit
Visit
Concomitant 
medications (n)
BP = blood pressure; cdiff = Clostridium difficile ; CMV = cytomegalovirus; Cx = Culture; d = day; CRP = C-reactive protein; ECG = electrocardiogram; ET = early termination; EX = exam; Flex = flexible; HR = heart rate; PCR = polymerase chain reaction; prep = preparation; RR = respiration rate; 
Sig = sigmoidoscopy; Wk = week; WOCBP = women of childbearing potential.
Notes:  (a) Height on screening only; BP, RR, HR, Temp and weight at all vital signs assessments; (b) Prior to dosing; (c) 1st dose observe 1 hr post-dosing; (d) As close to scheduled day as possible ; (e) Urinalysis will be performed by dipstick; If nitrates or leukocytes are positive, a microscopic 
examination will be performed by the central laboratory (f) Must be performed at least 3 days before Day 1; (g) Sample needs to be obtained and results reviewed prior to  lower endoscopy (flexible sigmoidoscopy or colonoscopy) ; (h) Obtain sample and hold.  Only samples from subjects that are 
randomized will be analyzed; (i) Clear liquid diet day before procedure with bowel prep at PI discretion (e.g. two Fleets enemas 1.5 hours before procedure); (j) Subjects who terminate pr ior to Visit 12 will have a lower endoscopy (flexible sigmoidoscopy or colonoscopy) at the Early Termination visit; 
(k) Beginning the night before the lower endoscopy (flexible sigmoidoscopy or colonoscopy); (l) Quantitative CMV testing on plasma; (n) Concomitant medications will be recorded from Week 12 through Day 246 only if they are associated with an AE; (o) Prior to randomization; (p) Following Visit 
13 throughDay 246/ET only SAEs, and concomitant medications associated with SAEs will be collected;  (q) Instruct subject to take study drug at the same time each day when possible
X
Total modified Mayo 
score
X
Adverse event 
reporting (p)
Visit/Phone Call
Visit
Visit for 
sigmoidoscopy(f
)
Visit
Visit
Stool sample
Visit
Stool sample
Visit
Phone call
Visit
Phone call
Short Term Safety Follow-up (Day 64 to 92 ) and a Long Term Safety 
Follow-up (Day 93-246). 
Visit 4
Visit 5
VISIT DAY
Day 1
Day 8 +/- 1d
Day 15 +/-1d
Day 22+/-1d
Day 29 +/-1d
Day 36 +/-1d
Day 43  +/-1d
Day 50 +/-1d
Day 57+/-1d
Day 64+/-3d
Weekly on 
Days 71, 78, 
85+/-2d
Day 92+/-2d
Screening with  lower 
endoscopy (flexible 
sigmoidoscopy or colonoscopy) 
(Day -17 to Day -1 )
Pre-Treatment 
Period (Day 1-7)

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  52 of 75                                                  10 Oct 2016  
7.2!
Procedures by Visit 
Visits should occur within ± 1 day of the scheduled visit. All times should be recorded 
using the 24-hour clock (e.g., 23:20, not 11:20 pm). 
7.2.1! Screening Day -17 to Day -1 (Visit 1) 
•! Obtain written informed consent for study; 
•! Verify conformance with inclusion/exclusion entry criteria; 
•! Record medical history; 
•! Record Demographics; 
•! Begin Adverse event monitoring; 
•! Record prior/concomitant medication history; 
•! Perform physical exam; 
•! Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, 
temperature); 
•! Obtain weight and height 
•! Blood sampling for hematology, clinical chemistry, C-reactive protein (CRP); 
•! Urinalysis; 
•! Blood sampling for quantitative cytomegalovirus (CMV) polymerase chain reaction 
(PCR) testing on plasma; 
•! Blood sampling for metabolomics, serum cytokines 
•! Blood sampling for pregnancy test for women of childbearing potential (WOCBP); 
•! Stool sampling for Clostridium difficile, microbiome, microbial culture, 
metabolomics, fecal calprotectin; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Obtain diet inventory; 
7.2.2! Screening Visit 2 Day -17 to Day -1 (Visit 2) 
•! Verify conformance with inclusion/exclusion entry criteria; 
•! Confirm subject has had no liquids 6 hours prior to lower endoscopy (flexible 
sigmoidoscopy or colonoscopy); 
•! Confirm subject performed bowel preparation at PI discretion (e.g., two Fleets 
enemas 1.5 hours before procedure); 
•! Perform lower endoscopy (flexible sigmoidoscopy or colonoscopy); 
•! Obtain biopsy for mucosal transcriptomics (2 samples); 
•! Obtain biopsy for histopathology with CMV stain (1 sample); 
•! Obtain biopsy for mucosal microbiome (1 sample); 
•! Obtain Partial Mayo score; scores should reflect the 24-hour period before initiation 
of bowel preparation. 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  53 of 75                                                  10 Oct 2016  
o! Partial Mayo score at Screening Visit 2 should be used when calculating 
the Total modified Mayo score to determine subject eligibility. 
•! Obtain Total modified Mayo score; 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.3! Pretreatment Period Day 1 (Visit 3) 
•! Perform central review of results prior to randomization; 
•! Confirm eligibility with Medical Monitor pre-randomization 
•! Perform randomization; 
•! Begin pre-treatment drug dosing (observe subject 1 hour post-dosing) 
•! Perform physical exam; 
•! Assess vital signs (systolic and diastolic blood pressure, respiratory rate, 
temperature); 
•! Obtain weight; 
•! Blood sampling pre-dose for hematology, clinical chemistry; 
•! Blood sampling pre-dose for biomedical research; 
•! Obtain urine sample for pregnancy testing; 
•! Dispense pre-treatment drug; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.4! Treatment Period Day 8 ± 1 (Visit 4) 
•! Pre-dosing 
o! Return any remaining pre-treatment drug and all bottles dispensed; 
o! Begin treatment period drug dosing (observe subject 1 hour post-dosing); 
o! Blood sampling pre-dose for hematology, clinical chemistry, C-reactive 
protein (CRP); 
o! Perform 12-lead ECG; 
o! Blood sampling pre-dose for metabolomics; 
o! Urinalysis; 
o! Stool sampling pre-dose for microbiome, microbial culture, 
metabolomics, fecal calprotectin; 
•! Dosing 
o! Dispense study drug; 
o! Obtain diet inventory; 
o! Obtain Partial Mayo score; 
o! Continue adverse event monitoring; 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  54 of 75                                                  10 Oct 2016  
o! Record concomitant medications. 
7.2.5! Treatment Period Day 11 (as close to scheduled day as possible) 
•! Study drug dosing; 
•! Stool sampling for microbiome, microbial culture; 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.6! Treatment Period Day 15 ± 1 (Visit 5) 
•! Return study drug; 
•! Dispense study drug 
•! Study drug dosing; 
•! Stool sampling for microbiome, microbial culture; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Continue adverse event monitoring; 
•! Record concomitant medications; 
•! Remind subject to begin overnight fast where possible the night prior to Visit 6. 
7.2.7! Treatment Period Day 18 (as close to scheduled day as possible) 
•! Study drug dosing; 
•! Stool sampling for microbiome, microbial culture; 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.8! Treatment Period Day 22 ± 1 (Visit 6) 
•! Return all unused study drug and any bottles dispensed; 
•! Dispense study drug; 
•! Study drug dosing; 
•! Perform physical exam; 
•! Blood sampling for C-reactive protein (CRP); 
•! Blood sampling for metabolomics; 
•! Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, 
temperature); 
•! Obtain weight; 
•! Stool sampling for microbiome, microbial culture, metabolomics, fecal calprotectin; 
•! Obtain diet inventory; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  55 of 75                                                  10 Oct 2016  
7.2.9! Treatment Period Day 29 ± 1 (Visit 7) 
•! Return all unused study drug and any bottles dispensed; 
•! Dispense study drug; 
•! Study drug dosing; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
•! Remind subject to begin overnight fast where possible the night prior to Visit 8; 
7.2.10! Treatment Period Day 36 ± 1 (Visit 8) 
•! Return all unused study drug and any bottles dispensed; 
•! Dispense study drug; 
•! Study drug dosing; 
•! Perform physical exam; 
•! Blood sampling for hematology, clinical chemistry, C-reactive protein (CRP); 
•! Blood sampling for metabolomics; 
•! Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, 
temperature); 
•! Obtain weight; 
•! Urinalysis; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.11! Treatment Period Day 43 ± 1 (Visit 9) 
•! Return all unused study drug and any bottles dispensed; 
•! Dispense study drug; 
•! Study drug dosing; 
•! Obtain Partial Mayo score; 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.12! Treatment Period Day 50 ± 1 (Visit 10) 
•! Return all unused study drug and any bottles dispensed; 
•! Dispense study drug; 
•! Study drug dosing; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Continue adverse event monitoring; 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  56 of 75                                                  10 Oct 2016  
•! Record concomitant medications. 
7.2.13! Treatment Period Day 57 ± 1 (Visit 11) 
•! Return all unused study drug and any bottles dispensed; 
•! Dispense study drug; 
•! Study drug dosing; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Continue adverse event monitoring; 
•! Record concomitant medications; 
•! Remind subject to begin overnight fast the night prior to the lower endoscopy 
(flexible sigmoidoscopy or colonoscopy). 
7.2.14! Follow-up Period Day 64 ± 3 (Visit 12)/Early Termination 
•! Return all unused study drug and any bottles dispensed; 
•! Perform physical exam; 
•! Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, 
temperature); 
•! Obtain weight; 
•! Confirm subject has had no liquids 6 hours prior to lower endoscopy (flexible 
sigmoidoscopy or colonoscopy); 
•! Confirm subject has performed bowel preparation at PI discretion (e.g. two Fleets 
enemas 1.5 hours before procedure); 
•! Perform lower endoscopy (flexible sigmoidoscopy or colonoscopy); 
•! Blood sampling for hematology, clinical chemistry, C-reactive protein (CRP); 
•! Urinalysis; 
•! Blood sampling for metabolomics, serum cytokines; 
•! Blood sampling for biomedical research; 
•! Obtain urine sample for pregnancy testing; 
•! Obtain biopsy for mucosal transcriptomics (2 samples); 
•! Obtain biopsy for histopathology with CMV stain (1 sample); 
•! Obtain biopsy for mucosal microbiome (1 sample); 
•! Stool sampling for microbiome, microbial culture, metabolomics, fecal calprotectin; 
•! Obtain diet inventory; 
•! Obtain Partial Mayo score; scores should reflect the 24-hour period before initiation 
of bowel preparation. 
•! Obtain Total modified Mayo score; 
•! Continue adverse event monitoring; 
•! Record concomitant medications; 
•! Remind subject to begin overnight fast where possible the night prior to Visit 13. 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  57 of 75                                                  10 Oct 2016  
7.2.15! Follow-up Period Day 71 ± 2 (Phone Call)  
•! Obtain Partial Mayo score; Physician Rating of Disease Activity not collected  
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.16! Follow-up Period Day 78 ± 2 (Phone Call)  
•! Obtain Partial Mayo score; Physician Rating of Disease Activity not collected  
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.17! Follow-up Period Day 85 ± 2 (Phone Call)  
•! Obtain Partial Mayo score; Physician Rating of Disease Activity not collected 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.18! Follow-up Period Day 92 ± 1 (Visit 13)  
•! Perform physical exam; 
•! Assess vital signs (systolic and diastolic blood pressure, respiratory rate, 
temperature); 
•! Obtain weight; 
•! Perform 12-lead ECG; 
•! Blood sampling for C-reactive protein (CRP); 
•! Blood sampling for metabolomics; 
•! Obtain urine sample for pregnancy testing; 
•! Stool sampling for microbiome, microbial culture, metabolomics, fecal calprotectin; 
•! Obtain Partial Mayo score; scores should reflect the prior 24 hours 
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
7.2.19! Early Termination Visit 
Subjects who discontinue early from the study before Visit 12 should, where possible, 
have an Early Termination visit. This visit should take place as soon as possible after the 
subject stops taking study drug. The observations and procedures scheduled for the 
Follow-Up Visit 12, including a urine pregnancy test, should be performed at the Early 
Termination visit. 
 
For subjects who terminate between Visit 12 and 13, the observations and procedures 
scheduled for the Follow-Up Visit 13 should be performed.   
7.2.20! Follow-up Period Day 246 ± 3 (Phone Call)  
•! Obtain Partial Mayo score; Physician Rating of Disease Activity not collected 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  58 of 75                                                  10 Oct 2016  
•! Continue adverse event monitoring; 
•! Record concomitant medications. 
 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  59 of 75                                                  10 Oct 2016  
8!
STATISTICAL METHODS 
This study has a primary study period (from Visit 1 through Visit 13) followed by a long 
term safety follow-up period to Day 246.  The primary study period will be conducted as 
a double-blind study.  The final database for the primary study period will remain 
blinded until all data collected through Visit 13 has been entered, cleaned and declared 
complete and final.  The CSR will be finalized after results from the primary study period 
are complete; all available data post-Visit 13 pertaining to mortality will be provided.  
Results of the long term safety period (through Day 246) will be presented in a separate 
report. 
 
Before the primary study period data is declared complete and final, a statistical analysis 
plan (SAP) will be issued as a separate document, providing detailed methods for the 
analyses outlined below.  Any deviations from the planned analyses will be described 
and justified in the final integrated clinical study report. 
8.1!
Study Subjects 
8.1.1! Disposition of Subjects 
The number and percentage of subjects entering and completing the clinical study will be 
presented, by treatment group. 
8.1.2! Protocol Deviations 
Protocol deviations will be listed by subject. 
8.1.3! Analysis Sets 
Safety Population: 
The Safety Population will consist of all subjects 
who receive any amount of study drug.  Subjects 
will be analyzed according to the treatment they 
actually received, rather than the treatment to which 
they were randomly assigned.  All safety analyses 
will be conducted based on the Safety Population. 
Intent-to-Treat Analysis Population: The Intent-to-Treat (ITT) Population will consist of 
all subjects who were randomly assigned, including 
those who were not exposed to any study drug, and 
will be analyzed based on the treatment to which 
they were randomly assigned.   
Modified Intent-to-Treat Population: The modified Intent-to-Treat (mITT) Population 
will consist of all randomized patients with baseline 
and at least one post-baseline stool sample, 
including those who were not exposed to any study 
drug, and will be analyzed based on the treatment to 
which they were randomized.   
All clinical response analyses will be conducted in the ITT population and in the mITT 
population as sensitivity analyses. 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  60 of 75                                                  10 Oct 2016  
All microbiome alterations analyses will be conducted in the mITT population. 
8.2!
Endpoints for Analysis 
8.2.1! Endpoints and Analysis for Primary Objectives 
The primary endpoint for assessment of safety and tolerability will be AEs, classified to 
body system and preferred term as well as severity and causality. Other safety and 
tolerability endpoints are AESIs, laboratory evaluation results, vital sign measurements 
and physical examination findings. Safety endpoint will be summarized by treatment 
group and also for the pooled SER-287 treatments (A, C and D). The assessment of 
safety will be based on descriptive summaries of SER-287 treatment groups and the 
placebo treatment group. 
 
Composition of the microbiome at Visit 1, Visit 4, Visit 5, Visit 6, Visit 12, Visit 13, or 
at early termination will be measured in terms of both the total number of unique types of 
bacteria (i.e., α-diversity) and the microbial composition (i.e., β-diversity). Engraftment 
is defined as the germination and outgrowth of bacteria that comprise the SER-287 spore 
ecology in a subject’s gastrointestinal tract post-treatment. Engraftment will be assessed 
at time points between Visit 4 and Visit 13. 
 
Differences between changes in the microbiome across the various treatment arms will 
be evaluated using both non-parametric tests for α-diversity and multivariate analysis of 
variances of dissimilarity matrices for β-diversity. Dissimilarity will be defined by using 
the unweighted Unifrac dissimilarity metric, which evaluates changes in the overall 
phylogenetic composition between two samples; this method is widely used in the study 
of microbial communities and represents a balanced approach with minimal bias to the 
presence of low- and high-abundance bacteria.  
 
Additional measures of dissimilarity that are routinely used in the analysis of microbiome 
data sets will be further evaluated. 
8.2.2! Endpoints and Analysis for Secondary Objectives 
Efficacy response endpoints comprise clinical response, complete remission and 
endoscopic improvement. The primary time point for analysis is Visit 12. Estimates of 
the risk difference and confidence interval will be reported for treatment groups A, C and 
D separately compared to placebo. 
Serum biomarkers (CRP) and fecal biomarkers (fecal calprotectin) at Visit 1, Visit 4, 
Visit 6, Visit 12 and Visit 13 will be assessed using descriptive summary tables and 
treatment mean [+/- standard deviation (SD)] profile plots (response versus timepoint). 
8.2.3! Exploratory Endpoints 
All time points of exploratory endpoint will be listed and presented in descriptive 
summary tables. 
•! Stool and blood metabolic pathways 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  61 of 75                                                  10 Oct 2016  
•! Serum cytokine profile 
•! Mucosal transcriptomic profile 
•! Mucosal microbiome  
•! Mucosal Histopathology, including cytomegalovirus (CMV) Immunohistology 
stains 
•! Microbial Culture Endpoints: 
o! Candida titer and diversity 
8.3!
General Considerations 
8.3.1! Statistical Methods 
All safety and tolerability, intestinal microbiome, clinical efficacy, and biomarker data 
will be listed and presented in descriptive summaries by study arm, visit and time point. 
At a minimum, continuous data will be summarized by study arm using descriptive 
statistics (number, mean, SD minimum, median and maximum).  Categorical data will be 
summarized by study arm using frequency tables (number and percentage). 
Selected clinical response and biomarker data will be presented in treatment mean (+/-
SD) profile plots.   
8.3.2! Statistical Significance 
Statistical significance tests, if reported, will be two-sided and will be presented as 
relative measures of the strength of association to study arm for comparison among study 
endpoints.  All reported confidence intervals will be 95%, two-sided.  P-values and/or 
confidence intervals generated for this study are not intended to be conclusive, but 
provided for guidance only.  
In general, inferential analysis will be based on pairwise comparisons, A, C and D 
separately compared to placebo (B) and also the comparisons A versus D and C versus 
D. For continuous data these comparisons will be assessed using confidence intervals 
estimated using one-way analysis of variance (ANOVA) models fit to the separate results 
of each visit. For binary data these comparisons will be assessed by analysis of two-by-
two tables and calculation the risk difference and confidence interval. Additional details 
of the statistical analysis will be addressed in a statistical analysis plan, finalized prior to 
the time the primary study period (Visit 1 to Visit 13) data is declared complete and final 
and study unblinding. 
8.3.3! Missing or Spurious Data 
Any AE with incomplete date or time will be evaluated conservatively in the 
classification of treatment emergent AE.  Any apparently spurious data will be verified.  
No verified data will be excluded from summaries or analysis. 
 
Several missing imputation methods, such as worst case analyses, observed case analyses 
and last observation carried forward, will be applied to analyze the clinical efficacy 
endpoints. 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  62 of 75                                                  10 Oct 2016  
8.4!
Safety Analyses 
8.4.1! Adverse Events 
Adverse events will be coded by using the Medical Dictionary for Regulatory Activities 
(MedDRA). Summary tables of treatment-emergent adverse events (TEAEs) by 
treatment group will be provided. A TEAE is any AE that newly appeared, increased in 
frequency, or worsened in severity after initiation of study drug. A listing of all AEs, 
including those occurring before the start of study drug, will be provided. The percentage 
of subjects with TEAEs will be tabulated by system organ class (SOC) and preferred 
term (PT) for each treatment group. The incidence of TEAEs based on the number of 
days the subjects in each treatment group were on study drug (per subject on therapy 
day) will also be presented by system organ class and preferred term for each treatment 
group by severity, and by relationship to treatment. Tables of any TEAEs leading to 
study drug discontinuation, AESIs and SAEs will also be provided.  
8.4.2! Clinical Laboratory Tests 
All scheduled and unscheduled laboratory results will be presented for each subject, 
sorted by category, subject, test and sample time.  Flags will be attached to values outside 
of the laboratory’s reference limits along with the Investigator’s assessment.  A separate 
listing of abnormal results will be presented, ordered by test, subject and sample time.     
Quantitative chemistry and hematology tests (observed values and change from baseline) 
will be summarized descriptively in tabular format. A shift table will be presented for 
chemistry, hematology and urinalysis tests shift from baseline to each post-baseline visit 
and also the shift from baseline to highest and to lowest post-baseline assessment. 
8.4.3! Vital Signs 
Individual data listings of vital signs (observed and change from baseline) will be 
presented for each subject. Descriptive statistics of the vital signs will be presented by 
treatment group for all study visits at which they were collected. The change from 
baseline to each post-baseline visit will also be summarized by treatment group. 
8.4.4! Physical Examination Findings 
Abnormal clinically significant physical examination (PE) finding will be reported as 
medical history (MH) or as an AE.  
8.4.5! Pharmacokinetic Analyses  
Not applicable 
8.5!
Gastrointestinal Tract Microbiome 
The gastrointestinal (GI) microbiome of subjects will be characterized by using at 
minimum recombinant deoxyribonucleic acid (rDNA) 16S V4 genomic data sets 
generated from stool collected at the time points defined above for the various endpoints.  
Genomic data sets will define the microbial composition of the microbiome of a subject 
at a given time point. Genomic sequence read data sets will be analyzed to assign a 
taxonomic identity at the resolution of an operational taxonomic unit (OTU) and 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  63 of 75                                                  10 Oct 2016  
phylogenetic clade (clade) and, further, to define the relative proportion of each OTU and 
clade to all other OTUs and clades in a given sample.  
Changes in the composition of the microbiome will be measured and analyzed as 
described in Section 8.2.1. 
8.6!
Interim Analyses 
No interim analysis is planned for this study. 
8.7!
Determination of Sample Size 
No formal sample size calculation was performed.  A sample size of approximately 55 
subjects, with 15 subjects randomized to each of the active arms (Treatment Groups A, C 
and D) and 10 subjects in the placebo arm (Treatment Group B) is considered sufficient 
to evaluate the safety, microbiome alterations, clinical response and exploratory 
objectives of the study.  All comparisons performed in this study will be descriptive in 
nature. P-values and/or confidence intervals generated for this study are not intended to 
be conclusive, but are provided for guidance only. 
 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  64 of 75                                                  10 Oct 2016  
9!
ADMINISTRATIVE REQUIREMENTS  
9.1!
Good Clinical Practice 
The study will be conducted in accordance with the International Conference on 
Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and the appropriate 
regulatory requirement(s). The Investigator will be thoroughly familiar with the 
appropriate use of the Investigational product. Essential clinical documents will be 
maintained to demonstrate the validity of the study and integrity of the data collected. 
Master files will be established at the beginning of the study, maintained for the duration 
of the study, and retained according to the appropriate regulations. 
•! The Principal Investigator has the overall responsibility for the conduct and 
administration of the study at the clinical site and for contacts with the sponsor, the 
IRB/IEC, and local authorities. 
•! The Principal Investigator is responsible for ensuring the privacy, health, and welfare 
of the subjects during and after the clinical study.  
•! All Investigators are responsible for performing the study in accordance with the 
protocol and the above guidelines and regulations, and for collecting, documenting, 
and reporting the data accurately. 
•! All Investigators must be familiar with the background and requirements of the study 
and with the properties of the investigational product as described in the current 
version of the Investigator’s Brochure 
•! The Principal Investigator is responsible for distributing study information and 
documentation to all appropriate staff members before and during the course of the 
study as updated information becomes available. 
9.2!
Ethical Considerations 
The study will be conducted in accordance with ethical principles in the Belmont Report, 
and in compliance with local IRB/IEC requirements and institutional guidelines. 
The Investigator must obtain IRB/IEC approval of the protocol, ICF, and other required 
study documentation before starting the study. It is the responsibility of the Investigator 
to ensure that all aspects of IRB/IEC review are conducted in accordance with current 
governmental regulations. 
A progress report must be submitted to the IRB/IEC at the required intervals and not less 
than annually. At the completion or termination of the study, the Investigator must 
submit a closeout letter to the IRB/IEC. 
9.3!
Subject Information and Informed Consent 
Before any testing under this protocol, including screening tests and assessments, written 
informed consent with the IRB/IEC-approved ICF must be obtained from the subject in 
accordance with local practice and regulations. 
 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  65 of 75                                                  10 Oct 2016  
The background of the proposed study, procedures, and benefits and risks of the study 
must be explained to the subject. The subject must be given sufficient time to consider 
whether to participate in the study. 
A copy of the ICF, signed and dated by the subject, must be given to the subject. Each 
ICF should contain an authorization allowing the Investigator to use and disclose subject 
health information (i.e., subject-identifiable health information) in compliance with local 
law. 
9.4!
Subject Confidentiality 
Subject confidentiality is held strictly in trust by the Investigator and medical and 
laboratory staff. This confidentiality is extended to cover testing of biological samples in 
addition to the clinical information relating to participating subjects. The Investigator 
will grant regulatory authority(ies) access to the subject’s original medical records for 
verification of data gathered and to audit the data collection process. The subjects’ and 
donors’ confidentiality will be maintained and will not be made publicly available to the 
extent permitted by the applicable laws and regulations. 
 
Subjects will not be identified by name in any study reports, and these reports will be 
used for research purposes only. 
9.5!
Protocol Compliance 
The Investigator will conduct the study in compliance with the IRB/IEC-approved 
protocol without any changes or deviations. Modifications to the protocol will require 
approval from the sponsor and written IRB/IEC approval before implementation, except 
when the modification is needed to eliminate an immediate hazard to the subject. Any 
change, intentional or otherwise, must be reported immediately to the sponsor and to the 
relevant IRB/IEC and/or regulatory authority as required by guidelines or regulation. 
Sites that fail to comply may be terminated. 
9.6!
Future Use of Stored Specimens 
The sponsor may conduct future biomedical research on specimens (including blood and 
feces) routinely and specifically collected during this clinical study that may be used for 
potential commercial use by Seres Therapeutics and may be stored for up to 10 years. 
This research may include genetic analyses [deoxyribonucleic acid (DNA)] and/or the 
measurement of other analytes. 
9.7!
Study Monitoring 
Regular monitoring is defined in ICH Guidance for Industry E6 Good Clinical Practice: 
Consolidated Guidance, Section 1.38, as “The act of overseeing the progress of a clinical 
trial, and of ensuring that it is conducted, recorded, and reported in accordance with the 
protocol, standard operating procedures, Good Clinical Practice (GCP), and the 
applicable regulatory requirement(s).” The purpose of monitoring is to verify that: 
•! Rights and well-being of the human subjects are protected. 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  66 of 75                                                  10 Oct 2016  
•! The reported study data are accurate, complete, and verifiable from source 
documents. 
•! The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with the applicable regulatory requirements. 
It will be the responsibility of the Investigator to ensure that the essential documents are 
available at the Investigator or institutional site. Any or all of these documents may be 
pertinent to, and should be available for, monitoring by the sponsor or inspection by the 
regulatory authorities as defined in the monitoring plan. 
The sponsor or an authorized sponsor representative will conduct regular site monitoring 
visits to review and validate study data as defined in the monitoring plan by reviewing 
subjects’ medical records and eCRFs in accordance with written standard operating 
procedures, ICH guidelines, GCP, and applicable regulations and guidelines. The 
Investigator will allow representatives of the sponsor or regulatory authorities to inspect 
facilities and records relevant to this study. 
9.8!
Data and Safety Monitoring Committee 
To supplement the routine study monitoring outlined in this protocol, an external DSMC 
will monitor the safety data from this study. The members of the DSMC will not be 
involved with the study (i.e., they are not study investigators) and must have no 
competing interests that could affect their roles with respect to the study. The DSMC will 
include 2 clinicians experienced in Gastroenterology and a statistician. The DSMC will 
make recommendations to ensure both patient safety and the continued ethical integrity 
of the study. Specific details regarding the responsibilities and requirements for 
documentation will be described in a separate charter that is reviewed and approved by 
the DSMC.  
9.9!
Case Report Forms and Study Records 
Data will be collected for this study by using an eCRF. The Investigator and study site 
staff will receive training and support on the use of the eCRF. All eCRF data are to be 
completed by the study coordinator or other designated site personnel. All data entry, 
modification, or deletion will be recorded automatically in the electronic audit trail. All 
data changes will be clearly indicated with a means to locate prior values. A unique user 
identification and password will be assigned to all personnel approved to enter or change 
data to prevent unauthorized access to the data.  
 
All electronic data entered by the site (including the electronic audit trail) will be 
maintained or made available at the site in compliance with Title 21 Part 11 of the Code 
of Federal Regulations (CFR) and other applicable retention regulations. The 
computerized system is able to generate accurate and complete copies of records in paper 
or electronic form for inspection and review by applicable regulatory authorities, the 
IRB/IEC/Research Ethics Board, and auditors or other designees authorized by the 
sponsor.  
 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  67 of 75                                                  10 Oct 2016  
In addition to capturing the user identification as part of the audit trail for all data entry, 
the eCRF allows for application of electronic signatures. The Investigator or designated 
subInvestigator, after review of the data in the eCRF, will confirm the validity of each 
subject’s data by electronic signature. This electronic signature will be certified as 
outlined in 21 CFR Part 11. 
 
The sponsor will retain the original eCRF data and audit trail. An electronic or certified 
paper copy of all completed eCRF data, including query resolution correspondence, will 
be provided to the Investigator at the end of the study. 
9.10! Study Completion  
The sponsor requires the following data and materials to be submitted before a study can 
be considered complete or terminated:   
•! Laboratory findings, clinical data, and all special test results from informed consent 
through the End-of-Study Visit at Week 13 and the final phone call on Day 246 
•! Electronic CRFs properly completed by appropriate study personnel and signed and 
dated by the Investigator 
•! Complete study drug accountability records  
•! Copies of IRB/IEC approval and notification of the original protocol and of any 
protocol amendments, if appropriate 
•! A summary of the study prepared by the Investigator (an IRB/IEC summary letter is 
acceptable) 
 

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  68 of 75                                                  10 Oct 2016  
10! REFERENCE LIST 
Angelberger, S., Reinisch, W., Makristathis, A., Lichtenberger, C., Dejaco, C., Papay, P., 
Novacek, G., Trauner, M., Loy, A., and Berry, D. (2013). Temporal Bacterial 
Community Dynamics Vary Among Ulcerative Colitis Patients After Fecal Microbiota 
Transplantation. Am. J. Gastroenterol. 
Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., 
Yamasaki, S., Saito, T., Ohba, Y., et al. (2011). Induction of colonic regulatory T cells by 
indigenous Clostridium species. Science 331, 337–341. 
Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., 
Saito, T., Narushima, S., Hase, K., et al. (2013). Treg induction by a rationally selected 
mixture of Clostridia strains from the human microbiota. Nature 500, 232–236. 
Baumgart, M., Dogan, B., Rishniw, M., Weitzman, G., Bosworth, B., Yantiss, R., Orsi, 
R.H., Wiedmann, M., McDonough, P., Kim, S.G., et al. (2007). Culture independent 
analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel 
phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum. 
ISME J. 1, 403–418. 
Biedermann, L., Zeitz, J., Mwinyi, J., Sutter-Minder, E., Rehman, A., Ott, S.J., Steurer-
Stey, C., Frei, A., Frei, P., Scharl, M., et al. (2013). Smoking cessation induces profound 
changes in the composition of the intestinal microbiota in humans. PloS One 8, e59260. 
Biedermann, L., Brülisauer, K., Zeitz, J., Frei, P., Scharl, M., Vavricka, S.R., Fried, M., 
Loessner, M.J., Rogler, G., and Schuppler, M. (2014). Smoking cessation alters intestinal 
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Clinical Study Protocol 
Protocol # SERES-101 
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Clinical Study Protocol 
Protocol # SERES-101 
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Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a 
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Clinical Study Protocol 
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APPENDICES 
Appendix 1: Total Modified Mayo Score  
 
Stool Frequency  
0= Normal  
1= 1-2 stools/day more than normal  
2= 3-4 stools/day more than normal  
3= >4 stools/day more than normal 
 
Rectal Bleeding 
0= None 
1= Visible blood with stool less than half the time 
2= Visible blood with stool half of the time or more 
3= Passing blood alone 
 
Mucosal Appearance at Endoscopya  
0= Normal 
1= Mild disease (erythema, decreased vascular pattern)  
2= Moderate disease (marked erythema, absent vascular pattern, friability, erosions)  
3= Severe disease (spontaneous bleeding, ulcerations)  
 
Physician Rating of Disease Activity  
0= Normal 
1= Mild 
2= Moderate 
3= Severe 
a: The mucosal appearance at endoscopy is not included in the partial Mayo score  
  
 
 
 
 
 
 
Sutherland LR, Marin F, Greer S et al. 5-Aminosalicylic acid enema in the treatment of distal ulcerative 
colitis, proctosigmoiditis and proctitis. Gastroenterology 1987; 92: 1894-8. 
Sandborn WJ, Kamm MA, Lichtenstein GR, Lyne A, Butler T, Joseph RE. MMX Multi-Matrix System 
mesalazine for the induction of remission in patients with mild-to-moderate ulcerative colitis: a combined 
analysis of two randomized, double-blind, placebo-controlled trials. Aliment Pharmacol Ther  26 2007: 
205-215.   

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Amendment 3                                                                  73 of 75                                                  10 Oct 2016  
Appendix 2: Diet Inventory 
 
 
Did you eat or drink the 
following products in the 
last 7 days? 
If yes, how recently? 
 
*please 
choose 
only 
one 
response per category, from 
this column 
Example:  
Vegetables (salad, tomatoes, onions, greens, 
carrots, peppers, green beans, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
● Within 24 hrs, 1 to 2 times 
○ Within 24 hrs, 3 or more 
times
Tea or coffee no sugar and no sugar 
replacement 
 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Soft drinks, tea or coffee with sugar (corn 
syrup, maple syrup, cane sugar, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Diet soft drinks, tea or coffee with sugar 
substitute (Stevia, Equal, Splenda, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Fruit juice (orange, apple, cranberry, prune, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Water 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Alcohol (beer, brandy, spirits, hard liquor, wine, 
aperitif, etc.) 
 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Yogurt or other foods containing active 
bacterial cultures (kefir, sauerkraut, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Dairy (milk, cream, ice cream, cheese, cream 
cheese) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Probiotic (other than yogurt) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
 
 

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Protocol # SERES-101 
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Amendment 3                                                                  74 of 75                                                  10 Oct 2016  
Fruits (no juice) (Apples, raisins, bananas, 
oranges, strawberries, blueberries, etc. (frozen or 
fresh) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Vegetables (salad, tomatoes, onions, greens, 
carrots, peppers, green beans, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Beans (tofu, soy, soy burgers, lentils, Mexican 
beans, lima beans, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Whole grains (wheat, oats, brown rice, rye, 
quinoa, wheat bread, wheat pasta, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Starch (white rice, bread, pizza, potatoes, yam, 
cereals, pancakes, etc.)  
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Eggs 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Processed meat (other red meat and other white 
meat such as lunch meat, ham, salami, bologna, 
sausage, kielbasa, hotdog, bacon, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Red meat (beef, hamburger, pork, lamb) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
White meat (chicken, turkey, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Shellfish (shrimp, lobster scallops, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Fish (fish nuggets, breaded fish, fish cakes, 
salmon, tuna, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Sweets (pies, jam, chocolate, cake, cookies, etc.) 
○ No, I did not consume 
these products in the last 7 
days 
○ Within the past 4 to 7 days 
○ Within the past 2 to 3 days 
○ Within 24 hrs, 1 to 2 times  
○ Within 24 hrs, 3 or more 
times
Integrative HMP (iHMP Research Network Consortium. The Integrative Human Microbiome Project: 
Dynamic Analysis of Microbiome-Host omics profiles during periods of human health and disease. Cell Host 
Microbe. 2014; 16(3): 276-89.  

Sponsor Name 
Clinical Study Protocol 
Protocol # SERES-101 
CONFIDENTIAL 
 
Amendment 3                                                                  75 of 75                                                  10 Oct 2016  
 
Appendix 3: Montreal Classification of Extent of Ulcerative Colitis 
 
E1: Ulcerative Proctitis – Involvement limited to the rectum (proximal extent of 
inflammation is distal to the rectosimgoid junction  
 
E2: Left-sided UC (distal UC)—Involvement limited to a portion of the colorectum distal 
to the splenic flexure  
 
E3: Extensive UC (pancolitis)—Involvement extends proximal to the splenic flexure  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal Classification of Inflammatory Bowel 
Disease: Controversies, Consensus, and Implications.  Gut 2006; 55:749-53.