ECO-RESET: A Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Multicenter Study to Assess Efficacy and Safety of SER-287 in Adults With Active Mild-to-Moderate Ulcerative Colitis
Phase: PHASE2
Conditions: Ulcerative Colitis
Sponsor: Seres Therapeutics, Inc.



Seres Therapeutics, Inc. 
Clinical Study Protocol 
Protocol # SERES-201 
CONFIDENTIAL 
Amendment 3 
4 of 116 
08-Oct-2019
Declaration of the Investigator 
Title: ECO-RESET: A Phase 2B, Randomized, Double-Blind, Placebo-Controlled, 
Multiple Dose, Multicenter Study to Assess Efficacy and Safety of SER‑287 in 
Adults with Active Mild-to-Moderate Ulcerative Colitis 
I have received and read the SERES-201 Protocol dated 08-October-2019 and agree to 
conduct the study as outlined.  I agree to maintain the confidentiality of all information 
received or developed in connection with this protocol.   
_____________________________________ 
_____________________ 
Printed Name of Investigator 
Date 
_____________________________________ 
Signature of Investigator 

Seres Therapeutics, Inc. 
Clinical Study Protocol 
Protocol # SERES-201 
CONFIDENTIAL 
Amendment 3 
5 of 116 
08-Oct-2019
PROTOCOL SYNOPSIS  
Title 
ECO-RESET: A Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, 
Multicenter Study to Assess Efficacy and Safety of SER‑287 in Adults with Active Mild-to-Moderate 
Ulcerative Colitis 
Sponsor 
Seres Therapeutics, Inc. 
Active Ingredient 
SER-287 (Eubacterial Spores, Purified Suspension, Encapsulated) 
Phase 
2B 
Sponsor Study 
No. 
SERES-201 
Population 
Male or female adult subjects 18-80 years of age, inclusive, with active mild-to-moderate Ulcerative 
Colitis 
Number of 
Subjects 
Approximately 201 subjects will be enrolled, approximately 67 subjects in each of three (3) treatment 
arms 
Study Centers 
Approximately 104 study centers in North America 
Planned 
Enrollment 
Duration: 
Approximately 17 months 
Objectives 
Primary Objective: 
•
To demonstrate the efficacy of SER-287, after 10 weeks of induction dosing (following
vancomycin pre-treatment), in achieving clinical remission
Key Secondary Objectives: 
•
To demonstrate the efficacy of SER-287, after 10 weeks of step-down induction dosing
(following vancomycin pre-treatment), in achieving clinical remission
•
To demonstrate the efficacy of SER-287, after 10 weeks of induction dosing (following
vancomycin pre-treatment), in achieving endoscopic improvement
•
To demonstrate the efficacy of SER-287, after 10 weeks of step-down induction dosing
(following vancomycin pre-treatment), in achieving endoscopic improvement
Other Secondary Objectives: 
•
To demonstrate the efficacy of each SER-287 treatment arm in achieving endoscopic remission
after 10 weeks of induction treatment
•
To demonstrate the efficacy of each SER-287 treatment arm in achieving histological mucosal
healing after 10 weeks of induction treatment
•
To demonstrate the efficacy of each SER-287 treatment arm in achieving clinical remission with
normalization of stool frequency after 10 weeks of induction treatment
•
To evaluate the efficacy of each SER-287 treatment arm on symptomatic remission (rectal
bleeding and stool frequency) after 10 weeks of induction treatment
•
To evaluate the engraftment of SER-287 bacteria from each SER-287 treatment arm into the
intestinal microbial community over time
•
For EMA consideration only (see Section 3, Definitions):
o
To demonstrate the efficacy of SER-287 to induce clinical remission, using less
stringent definition
o
To demonstrate the efficacy of SER-287 to induce clinical remission, using more
stringent definition
o
To demonstrate the efficacy of SER-287 to induce symptomatic remission and
endoscopic remission as co-endpoints
Safety Objective: 
To evaluate safety and tolerability of SER-287 

Seres Therapeutics, Inc. 
Clinical Study Protocol 
Protocol # SERES-201 
CONFIDENTIAL 
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Exploratory Objectives: 
•
To evaluate clinical remission at the end of maintenance treatment
•
To evaluate endoscopic remission at the end of maintenance treatment
•
To evaluate histological mucosal healing at the end of maintenance treatment
•
To evaluate clinical remission at the end of open-label treatment
•
To evaluate endoscopic improvement at the end of open-label treatment
•
To evaluate endoscopic remission at the end of open-label treatment
•
To evaluate histological mucosal healing at the end of open-label treatment
•
To evaluate the effect of SER-287 treatment on symptomatic remission (rectal bleeding and stool
frequency) over time
•
To evaluate the clinical remission rate of SER-287, by donor, after 10 weeks of induction
treatment
•
To assess improvement in quality of life, as measured by the Inflammatory Bowel Disease
Questionnaire (IBDQ)
•
To assess changes in serum biomarkers (C-reactive protein [CRP]) and fecal biomarkers (fecal
calprotectin)
•
To evaluate changes in the composition of the intestinal microbiome over time
•
To evaluate changes in signatures of host and microbial functional responses over time
Efficacy 
Endpoints 
Primary Endpoint (See Section 3, Definitions): 
•
Clinical remission with SER-287, after 10 weeks of induction dosing, following vancomycin
pre-treatment (Treatment Arm B), compared to placebo, following placebo pre-treatment
(Treatment Arm A)
Key Secondary Endpoints (See Section 3, Definitions): 
•
Clinical remission with SER-287, after 10 weeks of step-down induction dosing, following
vancomycin pre-treatment (Treatment Arm C), compared to placebo, following placebo pre-
treatment (Treatment Arm A)
•
Endoscopic improvement with SER-287, after 10 weeks of induction dosing, following
vancomycin pre-treatment (Treatment Arm B), compared to placebo, following placebo pre-
treatment (Treatment Arm A)
•
Endoscopic improvement with SER-287, after 10 weeks of step-down induction dosing,
following vancomycin pre-treatment (Treatment Arm C), compared to placebo, following
placebo pre-treatment (Treatment Arm A)
Other Secondary Endpoints (See Section 3, Definitions): 
•
Endoscopic remission after 10 weeks of induction treatment
•
Histological mucosal healing after 10 weeks of induction treatment
•
Clinical remission with normalization of stool frequency after 10 weeks of induction
treatment
•
Symptomatic remission (rectal bleeding and stool frequency) after 10 weeks of induction
treatment
•
Engraftment of SER-287 bacteria over time
•
For EMA consideration only (See Section 3, Definitions):
o
Clinical remission (less stringent criteria) after 10 weeks of induction treatment
o
Clinical remission (more stringent criteria) after 10 weeks of induction treatment
o
Clinical remission co-endpoints: symptomatic remission and endoscopic remission
after 10 weeks of induction treatment
Exploratory Endpoints (See Section 3, Definitions): 
•
Clinical remission at the end of maintenance treatment and at the end of open-label
treatment
•
Endoscopic improvement at the end of open-label treatment

Seres Therapeutics, Inc. 
Clinical Study Protocol 
Protocol # SERES-201 
CONFIDENTIAL 
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•
Endoscopic remission at the end of maintenance treatment and at the end of open-label
treatment
•
Histological mucosal healing at the end of maintenance treatment and at the end of open-
label treatment
•
Symptomatic remission (rectal bleeding and stool frequency) over time
•
Clinical remission after 10 weeks of induction treatment for each SER-287 donor used in the
induction treatment period
•
IBDQ scores after 10 weeks of induction, at the end of maintenance treatment, and at the
end of open-label treatment
•
Serum biomarkers: CRP after 10 weeks of induction treatment (Week 11), at the end of
maintenance treatment and at the end of open-label treatment
•
Fecal biomarkers: fecal calprotectin levels after 10 weeks of induction treatment (Week 11),
at the end of maintenance treatment and at the end of open-label treatment
•
Composition of the intestinal microbiome through the end of the maintenance treatment and
open-label treatment periods
•
Signatures of host and microbial functional responses through the end of the maintenance
treatment and open-label treatment periods
Evaluation of 
Safety 
The evaluation of safety data will be performed by comparing various safety parameters across 
treatment arms.  The following safety endpoints will be measured: 
•
Incidence of AEs, SAEs and AESIs
•
Laboratory evaluation results
•
Vital sign measurements
•
Physical examination findings
Incidence of AEs, SAEs and AESIs will be summarized for each SER-287 donor overall and within 
each treatment arm. 
Safety endpoints will be summarized at the end of the pre-treatment period (Week 1), Week 3, Week 
7, after 10 weeks of induction treatment (Week 11), at the end of maintenance treatment or open-
label treatment and at end-of-study. 
Study Design 
This is a Phase 2B, randomized, double-blind, placebo-controlled, multiple dose, multicenter study 
designed to evaluate the efficacy and safety of SER-287 in adult subjects, 18-80 years of age, 
inclusive, with active mild-to-moderate ulcerative colitis (UC).  
Approximately 201 subjects will be enrolled.  Enrollment in this trial, as well as the clinical 
endpoints, will be based upon a composite Three-Component Modified Mayo Score of 3 to 7, 
inclusive, which sums patient-reported rectal bleeding and stool frequency subscores with endoscopic 
subscore.  Endoscopic subscores will be determined by local and independent, blinded central 
readers.  The endoscopy central readers will remain blinded to subjects’ treatment assignments 
throughout the entire study. 
The key study phases after Screening and randomization are: Induction Treatment (three [3] 
treatment arms), Maintenance Treatment (for Remitters) or an Open-Label Extension Arm (for Non-
Remitters), and Long-Term Safety Follow-Up: 

Seres Therapeutics, Inc. 
Clinical Study Protocol 
Protocol # SERES-201 
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08-Oct-2019
reader will remain blinded to treatment assignment.  Subjects who experience a UC 
flare during the Open-Label treatment period will discontinue study drug and will 
be followed for safety for 26 weeks. 
5.
Long-Term Safety Follow-Up: All subjects will be followed for long-term safety for 26
weeks following their last treatment dose.  No office visits are required during this period.
Site personnel will conduct follow-up phone calls every four (4) weeks.  During the first
four (4) weeks of the Long-Term Safety Follow-Up Period, AEs/SAEs/AESIs, concomitant
procedures, and concomitant medications will be collected.  During subsequent follow-up
phone calls, subjects will be asked about any SAEs/AESIs and any concomitant medications
associated with an SAE/AESI.  Concomitant UC medications and UC procedures, and any
changes to these, will be collected throughout the entirety of the Long-Term Safety Follow-
Up Period.
Inclusion Criteria 
1.
Signed informed consent prior to initiation of any study-specific procedure or treatment.
The subject must be willing to provide written informed consent and understand the
potential risks and benefits from study enrollment and treatment.  The subject must also be
willing and able to comply with the scheduled visits, treatment plan, laboratory tests, daily
eDiary and other study procedures.
2.
Male or female (non-lactating), 18-80 years of age, inclusive
3.
Documented diagnosis of ulcerative colitis at least three (3) months prior to Screening.
Documentation should include lower endoscopic (flexible sigmoidoscopy or colonoscopy)
evidence or histological evidence (biopsy report) of UC; however, UC medical treatment
records may be sufficient, as determined by the PI.  Subjects must also have a minimum
disease extent of 15 cm from the anal verge, as determined at the Screening endoscopy.
4.
Active mild-to-moderate UC as determined by a Three-Component Modified Mayo Score of
3 to 7, inclusive, composed of endoscopic subscore (≥ 1, as determined by local and central
reader scores, with adjudication by a second central reader, if necessary), stool frequency
subscore (≥ 1) and rectal bleeding subscore (no eligibility requirement).  There will be a
maximum time of seven (7) business days between the Screening endoscopy and
randomization.
5.
Subjects must be willing to undergo a lower endoscopy (flexible sigmoidoscopy or
colonoscopy), including biopsy sample collection, at all specified timepoints.
6.
Subjects with an inadequate response to, loss of response to, or intolerance of, at least one
(1) of the following conventional therapies: 5-ASA compounds, corticosteroids, 6-
mercaptopurine (6-MP) or azathioprine (AZA), anti-TNFα, anti-integrin or tofacitinib (note
full definition within Section 5.1, Inclusion Criteria)
7.
If female, is either:
a.
Not of childbearing potential, defined as postmenopausal (≥ 12 continuous months
of amenorrhea with no other cause than menopause) or surgically sterile due to
bilateral tubal ligation, bilateral oophorectomy, or hysterectomy
b.
Of childbearing potential and participates in any activity associated with risk of
pregnancy: is practicing at least one (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 one (1) of the above methods for the
duration of the study.
8.
If male and partner is of childbearing potential, subject agrees to practice at least one (1)
highly effective method of birth control for the duration of the study.
Exclusion Criteria 
1.
Known history of Crohn’s disease
2.
No previous history of treatment for UC (treatment-naïve subjects should not be enrolled)
3.
Subjects on steroid medication (e.g. prednisone, budesonide, budesonide MMX®) who are
unable to have steroids tapered, and be completely off steroids at least two (2) weeks prior
to Screening

Seres Therapeutics, Inc. 
Clinical Study Protocol 
Protocol # SERES-201 
CONFIDENTIAL 
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4.
Subjects who have received any investigational or approved biologic therapy
(e.g. infliximab, adalimumab, golimumab, certolizumab, vedolizumab, ustekinumab,
natalizumab) within eight (8) weeks prior to Screening or five (5) half-lives prior to
Screening (whichever is longer)
5.
Subjects who have received any investigational or approved non-biologic therapy
(e.g. cyclosporine, tacrolimus, thalidomide, methotrexate, tofacitinib), except for those
specifically listed in the Permitted Concomitant Medications (e.g. stable dose of 6-
mercaptopurine, azathioprine, methotrexate for ≥ 12 weeks prior to Screening), for the
treatment of underlying disease, within 30 days or five (5) half-lives prior to Screening
(whichever is longer)
6.
Major gastrointestinal surgery (not including appendectomy or cholecystectomy) within two
(2) months before Screening, or any history of total colectomy
7.
Subjects with active celiac disease (i.e., active diarrhea due to documented celiac disease)
8.
Subjects with evidence of, or treatment for, Clostridium difficile infection, or other intestinal
pathogen, within 30 days prior to Screening
9.
Subjects with Clostridium difficile positive stool, performed with a toxin enzyme
immunoassay (EIA) by the Central Laboratory.  Subjects who test positive for C. difficile
can be treated with standard of care antibiotics and rescreened for the study after 30 days, as
per Exclusion Criterion #8.
10. Oral antibiotic use within 30 days before Screening
11. Expected to receive antibiotics (i.e., for planned/anticipated procedure) within the Induction
Treatment period
12. Received an investigational drug or live vaccine within two (2) months before Screening
13. Previously enrolled in a Seres Therapeutics SER-109 or SER-287 study
14. Received a fecal microbiota transplant (FMT; includes human microbiota-based
therapeutics) within three (3) months prior to Screening
15. 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.
Known hypogammaglobulinemia
b.
Known severe immunodeficiency
c.
Underlying liver function test (LFT) [Screening alanine aminotransferase (ALT) or
aspartate aminotransferase (AST)] abnormalities greater than 3x upper limit of
normal (ULN)
d.
Absolute neutrophil count (ANC) < 500 cells/mm3
e.
Hemoglobin levels < 9 g/dL
16. Subjects with anatomic or medical contraindications to lower endoscopy (flexible
sigmoidoscopy or colonoscopy), including but not necessarily limited to toxic megacolon,
gastrointestinal 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)
17. Unable to stop steroid enemas or suppositories, or 5-ASA enemas or suppositories, at least
two (2) weeks prior to Screening
18. Unable to stop probiotic treatment at least one (1) week prior to Screening.  Note: food
containing probiotics are permitted.
19. Known active malignancy, except for basal cell skin cancer or squamous cell skin cancer, or
concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active
malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation
with medical monitor)
20. Unable to comply with the protocol requirements, including the ability to take oral drugs; or
any condition that, in the opinion of the investigator, might interfere with study objectives or
compromise patient safety, including if the subject is likely to require surgery for UC during
the study period
21. Known allergy or intolerance to oral vancomycin
22. Current or recent history (six [6] months prior to Screening) of drug or alcohol abuse

Seres Therapeutics, Inc. 
Clinical Study Protocol 
Protocol # SERES-201 
CONFIDENTIAL 
Amendment 3 
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Concomitant 
Medications 
Permitted Concomitant Medications: 
The below medications are allowed at study entry.  Doses must remain stable during the study 
treatment period. 
1.
Oral aminosalicylates (if taken for at least six [6] weeks prior to Screening, with a stable
dose for ≥ 2 weeks prior to Screening)
2.
Immunomodulator: 6-Mercaptopurine, Azathioprine, Methotrexate (Stable dose for ≥ 12
weeks prior to Screening)
3.
Pain medication (stable dose), including low-dose aspirin (81 mg); Note: temporary use of
pain medication is permitted during the treatment period (e.g. for minor surgery), and is
defined as no more than 48 hours.  Temporary use of opiates should be discussed with the
medical monitor.
4.
Inhaled steroids for non-UC-related treatment (taper-down is also acceptable)
5.
Inactivated influenza vaccine
Prohibited Concomitant Medications and Nutritional Supplements: 
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 
drug administration. 
1.
Oral, intravenous (IV) and rectal steroids (e.g. prednisone, budesonide, budesonide MMX®)
2.
5-ASA enemas or suppositories
3.
Any investigational or approved biologic therapy (e.g. infliximab, adalimumab, golimumab,
certolizumab, vedolizumab, ustekinumab, natalizumab)
4.
Any investigational or approved non-biologic therapy (e.g. cyclosporine, tacrolimus,
thalidomide, methotrexate, tofacitinib)
5.
Anti-diarrheals (e.g. loperamide, diphenoxylate/atropine, or bile-salt sequestrant
[cholestyramine, colesevelam])
6.
Probiotics (food containing probiotics are permitted)
7.
Use of any nutritional supplement which claims to support or promote gut health should be
determined by medical monitor.
Statistical 
Methods 
Analysis Populations 
The Intent-to-Treat (ITT) Population will consist of all subjects who are randomly assigned, 
including those who are not exposed to any study drug, and will be analyzed based on the treatment 
to which they were randomized.  The ITT population will be the primary analysis population for all 
efficacy endpoints. 
The Modified Intent-to-Treat 1 (mITT-1) Population will consist of all randomized subjects with a 
baseline evaluation, who have active mild-to-moderate UC and receive any amount of study drug, 
and will be analyzed based on the treatment to which they were randomized. 
The Modified Intent-to-Treat 2 (mITT-2) Population will consist of all randomized subjects with a 
baseline evaluation, who have active mild-to-moderate UC and receive any amount of study drug, 
and will be analyzed based on the treatment to which they are randomized.  Subjects who are 
confirmed to have normal histology at baseline will be excluded from this analysis population.   
The Per Protocol (PP) Population will consist of subjects from the mITT-2 Population who do not 
have any major protocol deviations.  The details of the PP Population will be provided in the 
Statistical Analysis Plan (SAP) and defined before unblinding of the data. 
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 are randomly assigned.  All safety analyses will be conducted based on the Safety Population. 

Seres Therapeutics, Inc. 
Clinical Study Protocol 
Protocol # SERES-201 
CONFIDENTIAL 
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08-Oct-2019
The Microbiome Modified Intent-to-Treat (mcITT) Population will be used for analysis of 
microbiome data. It will consist of all randomized subjects with an evaluable stool sample collected 
at baseline, and at least one (1) evaluable stool sample collected after the start of dosing, who are 
exposed to any amount of study drug, and will be analyzed based on the treatment to which they are 
randomized. 
Analysis of the Primary Efficacy Endpoint 
The primary efficacy outcome measure for this study will be the difference in clinical remission rates 
after 10 weeks of induction treatment between SER-287 (Induction Dose after pre-treatment with 
vancomycin – Arm B) and placebo (Arm A).  The primary efficacy endpoint analysis will be based 
on the Cochran-Mantel-Haenszel (CMH) test, stratified by endoscopic score at baseline (1-2 vs. 3), 
and UC medications at baseline (5-ASA alone vs. immunomodulators with or without 5-ASA vs. 
none) in the ITT population. 
Analysis of the Key Secondary Efficacy Endpoints 
The key secondary efficacy endpoints will be analyzed using the same method used for the primary 
efficacy endpoint. 
Sensitivity Analyses for the primary and key secondary endpoint will be performed in the mITT-1, 
mITT-2, PP and Safety populations. 
Multiplicity Adjustment  
Adjustments for multiple testing will be made to test the primary efficacy and key secondary efficacy 
endpoints.  A fixed-sequence method will be used to maintain a study-wide 2-sided Type I error rate 
of 0.05.  Testing of the key hypotheses will be conducted in the following order, all at the same 
significance level (2-sided α = 0.05): 
1.
H01: No difference in clinical remission rates after 10 weeks of induction treatment between
Arm B (SER-287 at Induction Dose after pre-treatment with vancomycin) vs. Arm A (pre-
treatment with placebo followed by treatment with placebo) in the ITT population
2.
H02: No difference in clinical remission rates after 10 weeks of induction treatment between
Arm C (SER-287 at Step-Down Induction Dose after pre-treatment with vancomycin) vs.
Arm A (pre-treatment with placebo followed by treatment with placebo) in the ITT
population
3.
H03: No difference in endoscopic improvement rates after 10 weeks of induction treatment
between Arm B (SER-287 at Induction Dose after pre-treatment with vancomycin) vs. Arm
A (pre-treatment with placebo followed by treatment with placebo) in the ITT population
4.
H04: No difference in endoscopic improvement rates after 10 weeks of induction treatment
between Arm C (SER-287 at Step-Down Induction Dose after pre-treatment with
vancomycin) vs. Arm A (pre-treatment with placebo followed by treatment with placebo) in
the ITT population
Testing of later hypotheses in the sequence stops as soon as failure to show statistical significance at 
the 2-sided 0.05 level is observed in a hypothesis earlier in the sequence. 
Determination of Sample Size 
The planned sample size for this study is 67 subjects per treatment arm for a total sample size of 
201 subjects.  Assuming a clinical remission rate of 29% in the SER-287 arms and a clinical 
remission rate of 9% in the placebo arm, this sample size will provide 86% power to detect a 
difference of 20% in clinical remission rates between SER-287 to placebo, using a 2-sided 
significance level of 0.05. 

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Clinical Study Protocol 
Protocol # SERES-201 
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Table 1: 
Schedule of Events: Induction Treatment 
Screening 
Pre-
Treatment 
Induction Treatment Period - 10 Weeks 
Long-Term Safety 
Follow-Upo 
Unscheduled 
Visit/EoTn 
WEEK NUMBER 
Week -4 to -1 
Week 0 
Week 1
+/-1d 
Week 3
+3d
Week 7
+3d
Week 11
+3d
Every 4 Weeks to 
Week 37/EoSm
+/-3d 
VISIT NUMBER 
1 
2* 
3 
4 
5 
6 
7 
8-14 
Visit Type 
Clinic 
Clinic/Endoscopy 
(max. 7 days between 
endoscopy and randomization) 
Clinic 
Clinic 
Clinic 
Clinic 
Clinic/ 
Endoscopy 
Phone Calls 
Clinic 
(may include 
endoscopy) 
Procedure/Assessments 
Informed Consent 
X 
Inclusion/ Exclusion Criteria 
X 
X 
Medical History 
X 
UC History 
X 
Prior Medications & UC Therapies 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Procedures for UC a 
X 
X 
X 
X 
X 
X 
X 
X 
Demographic Data 
X 
Full Physical Exam 
X 
Focused Physical Exam 
Xi 
X 
X 
Vital signs  
X 
Xi 
X 
X 
Height (at Screening only), Weight 
X 
X 
X 
X 
Review lower endoscopy preparation instructions 
with subject prior to lower endoscopyb 
X 
X 
X 
Lower Endoscopy (Local and Central Reads) 
X 
X 
X 
Biopsies (4 samples) 
X 
X 
X 
Three-Component Modified Mayo Score c 
X 
X 
X 
IXRS Randomization 
X 
Dispense pre-treatment study drug 
Xg 
Administer study drug at clinic 
Xg 
Xg 
Return unused study drug 
X 
X 
X 
X 
X 
Review study drug compliance 
X 
X 
X 
X 
X 
Dispense study drug d 
Xj 
Xj 
Xj 
Adverse Event monitoring 
Xh 
X 
X 
X 
X 
Xl 
X 
Clinical Laboratory Tests 
Hematology 
X 
X i 
Xi 
X 
X 
Blood chemistry 
X 
Xi 
Xi 
X 
X 
Blood for CRP 
Xi 
X 
X 
Blood & Serum for Future Biomedical Research 
X 
X 
X 
X 
Urine Pregnancy test (WOCBP only) Note: Serum 
at Screening visit only 
X 
Xi 
Xi 
X 
X 
X 
X 
Routine Urine Dipsticke 
X 

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Clinical Study Protocol 
Protocol # SERES-201 
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Table 1: 
Schedule of Events: Induction Treatment (continued) 
Screening 
Pre-
Treatment 
Induction Treatment Period - 10 Weeks 
Long-Term Safety 
Follow-Upo 
Unscheduled 
Visit/EoTn 
WEEK NUMBER 
Week -4 to -1 
Week 0 
Week 1
+/-1d 
Week 3 
+3d
Week 7 
+3d
Week 11 
+3d
Every 4 Weeks to 
Week 37/EoSm
+/-3d 
VISIT NUMBER 
1 
2* 
3 
4 
5 
6 
7 
8-14 
Visit Type 
Clinic 
Clinic/Endoscopy 
(max. 7 days between 
endoscopy and randomization) 
Clinic 
Clinic 
Clinic 
Clinic 
Clinic/ 
Endoscopy 
Phone Calls 
Clinic 
(may include 
endoscopy) 
Procedure/Assessments 
Provide Stool Collection Kit 
X 
X 
X 
X 
X 
X 
Stool Sample for C. diff. testing by toxin assay 
(EIA) 
Xf 
Review Stool Collection, Handling & Storage 
Instructions with Subject 
X 
X 
X 
Stool Sample for Microbiome, Metabolomics, 
Future Biomedical Research 
Xf 
X 
X 
X 
Xk 
Xk 
Fecal Calprotectin 
Xf 
X 
X 
IBDQ 
X i 
X 
X 
Review Subject eDiary Instructions with Subject 
X 
Subject eDiary (daily rectal bleeding and stool 
frequency)  
X 
X 
X 
X 
X 
X 
X 
X 
Review Subject eDiary for compliance 
X 
X 
X 
X 
X 
X 
X 
(*) A minimum of seven (7) days between Visit 1 and Visit 2 are required to ensure there are a sufficient quantity of eDiary entries to calculate the Stool Frequency subscore; (a) Lower endoscopies 
performed during study are not to be recorded as a concomitant procedure; (b) Remind subjects when to start clear liquid diet, overnight fast, and bowel prep prior to scheduled lower endoscopy; 
(c) Three-Component Modified Mayo Score will be calculated electronically from subject diary and central endoscopy read; (d) Instruct subject to take study medication at the same time every morning;
At Screening Visit 1, subjects should be asked about their stool frequency and rectal bleeding over the past seven (7) days. Subjects will be provided an electronic diary at Screening Visit 1 to begin
daily collection of rectal bleeding & stool frequency; (e) Urine dipstick performed at the study site; if positive for nitrates and/or leukocytes, send sample to central laboratory for analysis; (f) If possible, 
subjects should provide stool sample on site.  If not possible, subject should collect stool sample at home and return to the site as soon as possible.  C. diff test results must be received before performing
lower endoscopy at Screening Visit 2;  Remind subjects when to start clear liquid diet, overnight fast, and bowel prep prior to scheduled lower endoscopy; (g) first dose observe for one (1) hour post-
dosing (h) Recording of AEs for study will begin after first dose of pre-treatment IP; (i) Perform prior to dosing; (j) IP to be dispensed at this clinic visit; (k) Stool sample to be collected prior to subject
starting clear liquid diet for lower endoscopy; (l) During the first four (4) weeks of the Long-Term Safety Follow-Up Period, AEs/SAEs/AESIs, concomitant procedures,  and concomitant medications
will be collected.  Only SAEs/AESIs and concomitant medications associated with the treatment of SAEs/AESIs will be collected starting from the four (4) week follow-up call through the End of
Study.  Concomitant UC medications and UC procedures, and any changes to these, will be collected throughout the entirety of the Long-Term Safety Follow-Up Period; (m) The last safety follow-up
call will occur after six (6) weeks, rather than four (4); (n) To accommodate scheduling of clinic visit and/or endoscopy, assessments & procedures for an Unscheduled Visit do not need to take place
during one (1) clinic visit; The Unscheduled Visit may also be used for dispensation of study drug as needed; For subjects who experience disease worsening (as defined in Section 3.6, Disease
Worsening), an Unscheduled Visit may be used by the PI to determine if the subject is experiencing a UC flare; The Unscheduled Visit can serve as an 'End of Treatment' visit for a subject who ends
treatment early in the study but will continue to be followed for safety, or for subjects who decide to leave the study early and not be followed for safety.  If subjects decide to end treatment early or
early terminate from the study, all study IP should be returned by the subject; (o) Subjects who discontinue early and do not go into either the Maintenance arm or Open Label arm, will be followed for
long term safety for 26 weeks post last study drug dose.

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Protocol # SERES-201 
CONFIDENTIAL 
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Table 2: 
Schedule of Events: Maintenance Treatment for Remitters 
Maintenance Treatment Period - 26 Weeks 
Long Term  
Safety Follow-Up 
Unscheduled 
Visit/EoT j
WEEK NUMBER
M-Week 12
+/-2d
M-Week 16
+3d
M-Week 20
+3d
M-Week 24
+3d
M-Week 28
+3d
M-Week 32
+3d
M-Week 37
+3d/EoT
Every 4 Weeks to 
M-Week 63/EoSh
+/-3d
VISIT NUMBER 
M-1
M-2
M-3
M-4
M-5
M-6
M-7
M-8 - M-13
Visit Type
Clinic
Clinic
Clinic
Clinic
Clinic
Clinic
Clinic/ 
Endoscopy
Phone Calls
Clinic 
(may include 
endoscopy) 
Procedure/Assessments 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Procedures for UCa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IXRS Re-Randomization 
X 
Focused Physical Exam 
X 
X 
X 
Vital signs  
X 
X 
Weight 
X 
Review lower endoscopy preparation 
instructions with subject prior to endoscopy b 
X
X
Lower Endoscopy (Local and Central Reads) 
X 
X 
Biopsies (4 samples) 
X 
X 
Three-Component Modified Mayo Scorec 
X 
X 
Return unused study drug 
X 
X 
X 
X 
X 
X 
X 
Review study drug compliance 
X 
X 
X 
X 
X 
X 
X 
Dispense study drugd 
X 
X 
X 
X 
X 
X 
Adverse Event monitoring 
X 
X 
X 
X 
X 
X 
X 
Xi 
X 
Clinical Laboratory Tests 
Hematology 
X 
X 
Blood chemistry 
X 
X 
Urine Pregnancy test (WOCBP only) 
X 
X 
X 
X 
X 
X 
X 
Blood & Serum for Future Biomedical 
Research 
X
X
Blood for CRP 
X 
X 

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Table 2: 
Schedule of Events: Maintenance Treatment for Remitters (continued) 
Maintenance Treatment Period - 26 Weeks
Long Term  
Safety Follow-Up
Unscheduled 
Visit/EoT j
WEEK NUMBER
M-Week 12
+/-2d
M-Week 16
+3d
M-Week 20
+3d
M-Week 24
+3d
M-Week 28
+3d
M-Week 32
+3d
M-Week 37
+3d/EoT
Every 4 Weeks to M-
Week 63/EoSh
+/-3d
VISIT NUMBER 
M-1
M-2
M-3
M-4
M-5
M-6
M-7
M-8 - M-13
Visit Type
Clinic
Clinic
Clinic
Clinic
Clinic
Clinic
Clinic/ 
Endoscopy
Phone Calls
Clinic 
(may include 
endoscopy) 
Procedure/Assessments 
Provide Stool Collection Kit 
X 
X 
X 
X 
X 
X 
Stool sample for Microbiome, 
Metabolomics, Future Biomedical 
Research 
X
X
X 
X 
X 
Xg
X
Fecal Calprotectin 
Xg 
X 
IBDQ 
X 
X 
Subject eDiary (daily rectal bleeding and 
stool frequency) e 
X
X
X
X
X
X
X
X
Review subject eDiary for compliance 
X 
X 
X 
X 
X 
X 
Xf 
X 
(a) Lower endoscopies performed during study are not to be recorded as concomitant procedure; (b) Remind subjects when to start clear liquid diet, overnight fast, and bowel prep prior to
scheduled lower endoscopy; (c) Three-Component Modified Mayo Score will be calculated electronically from subject diary and central endoscopy read;  (d) IP for weekly dosing will be
dispensed at this clinic visit; Instruct subject to take study drug at the same time every morning; (e) Subjects will continue using same electronic diary; (f) Subjects use of eDiary complete
at this visit; subject to leave device on site; (g) Stool sample to be collected prior to subject starting clear liquid diet for lower endoscopy. An aliquot for Fecal Calprotectin is taken from
this one stool sample collected at M-Week 37 visit; (h) The last safety follow-up call will occur after six (6) weeks, rather than four (4); (i) During the first four (4) weeks of the Long-Term
Safety Follow-Up Period, AEs/SAEs/AESIs, concomitant procedures, and concomitant medications will be collected.  Only SAEs/AESIs and concomitant medications associated with the
treatment of the SAEs/AESIs, will be collected starting from the four (4) week follow-up call through the End of Study. Concomitant UC medications and UC procedures, and any changes
to these, will be collected throughout the entirety of the  Long-Term Safety Follow-Up Period; (j) To accommodate scheduling of clinic visit and/or endoscopy, assessments & procedures
for an Unscheduled Visit do not need to take place during one (1) clinic visit; The Unscheduled Visit may also be used for dispensation of study drug as needed; For subjects who experience
disease worsening (as defined in Section 3.6, Disease Worsening), an Unscheduled Visit may be used by the PI to determine if the subject is experiencing a UC flare; The Unscheduled
Visit can serve as an 'End of Treatment' visit for a subject who ends treatment early in the study but will continue to be followed for safety, or for subjects who decide to leave the study
early and not be followed for safety.  If subjects decide to end treatment early or early terminate from the study, all study IP should be returned by the subject.

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Table 3: 
Schedule of Events: Open-Label Extension Arm for Non-Remitters 
Open-Label Treatment Period - 11 Weeks 
Long-Term Safety 
Follow-Up 
Unscheduled 
Visit/EoT k 
WEEK NUMBER 
OL-Week 0 
+/-2d 
OL-Week 1 
+/-1d 
OL-Week 3 
+3d
OL-Week 7 
+3d
OL-Week 11 
+3d
Every 4 Weeks for 
26 Weeks/EoSj
+/-3d 
VISIT NUMBER 
OL-1 
OL-2 
OL-3 
OL-4 
OL-5/EoT 
OL-6 – OL-11 
Visit Type 
Clinic 
Stool Sample 
Home 
Collection 
Clinic 
Clinic 
Clinic/ 
Endoscopy 
Phone Calls 
Clinic 
(may include 
endoscopy)
Procedure/Assessments 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Concomitant Procedures for UCa 
X 
X 
X 
X 
X 
X 
Focused Physical Exam 
X 
X 
Vital signs  
X 
X 
Weight 
X 
IXRS Registration for Open-Label 
X 
Dispense vancomycin pre-treatment 
X 
Administer vancomycin pre-treatment at clinic 
X 
Return unused study drug 
X 
X 
X 
X 
Review study drug compliance 
X 
X 
X 
Dispense SER-287 
Xe 
Xg 
Xg 
Adverse Event monitoring 
X 
X 
X 
X 
Xi 
X 
Clinical Laboratory Tests 
Hematology 
X 
X 
Blood chemistry 
X 
X 
Blood & Serum for Future Biomedical Research 
X 
X 
Blood for CRP 
X 
X 
Urine Pregnancy test (WOCBP) 
X 
X 
X 
X 
X 

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Protocol # SERES-201 
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Table 3: 
Schedule of Events: Open-Label Extension Arm for Non-Remitters (continued) 
Open-Label Treatment Period - 11 Weeks 
Long-Term Safety 
Follow-Up 
Unscheduled 
Visit/EoT k 
WEEK NUMBER 
OL-Week 0 
+/-2d 
OL-Week 1 
+/-1d 
OL-Week 3 
+3d
OL-Week 7 
+3d
OL-Week 
11 
+3d
Every 4 Weeks for 
26 Weeks/EoSj
+/-3d 
VISIT NUMBER 
OL-1 
OL-2 
OL-3 
OL-4 
OL-5/EoT 
OL-6 – OL-11 
Visit Type 
Clinic 
Stool Sample 
Home 
Collection 
Clinic 
Clinic 
Clinic/ 
Endoscopy 
Phone Calls 
Clinic 
(may include 
endoscopy)
Procedure/Assessments 
Provide Stool Collection Kit 
X 
X 
X 
X 
Stool sample for Microbiome, Metabolomics, Future 
Biomedical Research 
Xf 
X 
Xl 
X 
Fecal Calprotectin 
Xf 
X 
IBDQ 
X 
X 
Subject eDiary (daily rectal bleeding and stool frequency) b 
X 
X 
X 
X 
Xh 
X 
Review subject eDiary for compliance 
X 
X 
X 
X 
X 
Review lower endoscopy preparation instructions with 
subject prior to endoscopyc 
X 
X 
Lower Endoscopy (Local and Central Reads) 
X 
X 
Biopsies (4 samples) 
X 
X 
Three-Component Modified Mayo Scored 
X 
X 
(a) Lower endoscopies performed during study are not to be recorded as concomitant procedure; (b) Subjects will continue using same electronic diary;  Review pre-treatment
dosing and study drug dosing with subject; (c) Remind subjects when to start clear liquid diet, overnight fast, and bowel prep prior to scheduled lower endoscopy; Subjects will
return every four (4) weeks for re-supply of study drug that will be taken once-weekly; (d) Three-Component Modified Mayo Score will be calculated electronically from subject
diary and central endoscopy read;  (e) Two (2) weeks of IP is dispensed at clinic visit; subject should take Open-Label Week 3 dose on site; (f) Stool sample to be collected at
home.  Subject can return stool sample to clinic or it can be returned via courier to clinical site. An aliquot for Fecal Calprotectin is taken from this one stool sample collected at
OL-Week 11 visit; (g) IP is dispensed at this clinic visit; (h) Subjects use of eDiary complete at this visit; subject to leave device on site; (i) During the first four (4) weeks of the
Long-Term Safety Follow-Up Period, AEs/SAEs/AESIs, concomitant procedures, and concomitant medications will be collected.  Only SAEs/AESIs and concomitant medications
associated with the treatment of SAEs/AESIs will be collected starting from the four (4) week follow-up call through the End of Study.  Concomitant UC medications and UC
procedures, and any changes to these, will be collected throughout the entirety of the Long-Term Safety Follow-Up Period;  (j) The last safety follow-up call will occur after six
(6) weeks, rather than four (4); (k) To accommodate scheduling of clinic visit and/or endoscopy, assessments & procedures for an Unscheduled Visit do not need to take place
during one (1) clinic visit; The Unscheduled Visit may also be used for dispensation of study drug as needed; For subjects who experience disease worsening (as defined in Section
3.6, Disease Worsening), an Unscheduled Visit may be used by the PI to determine if the subject is experiencing a UC flare; The Unscheduled Visit can serve as an 'End of
Treatment' visit for a subject who ends treatment early in the study but will continue to be followed for safety, or for subjects who decide to leave the study early and not be
followed for safety.  If subjects decide to end treatment early or early terminate from the study, all study IP should be returned by the subject; (l) Stool sample to be collected prior
to subject starting clear liquid diet for lower endoscopy

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1 
Table of Contents 
PROTOCOL SYNOPSIS ................................................................................................. 5 
List of Study Personnel .................................................................................................. 22 
List of Abbreviations ...................................................................................................... 28 
1 
INTRODUCTION .................................................................................................. 31 
1.1 
Background ................................................................................................................ 31 
1.1.1 
Indication and Prevalence ........................................................................................ 31 
1.1.2 
Existing Practices .................................................................................................... 31 
1.1.3 
Disease Pathogenesis and Microbiome Involvement .............................................. 32 
1.1.4 
Pharmacological Concept for Microbiome Therapeutic .......................................... 33 
1.1.5 
Investigational Product ............................................................................................ 33 
1.2 
SER-287 SERES-101 Data in Active Mild-to-Moderate Subjects ......................... 33 
1.2.1 
Clinical Efficacy ...................................................................................................... 33 
1.2.2 
Clinical Safety ......................................................................................................... 35 
1.2.3 
Baseline Microbiome Composition ......................................................................... 36 
1.2.4 
Microbiome Engraftment and Post-Baseline Composition ..................................... 36 
1.3 
Phase 2B Overview ..................................................................................................... 38 
1.4 
Rationale ..................................................................................................................... 40 
1.4.1 
Rationale for Induction Dosing Regimen ................................................................ 40 
1.4.2 
Rationale for Maintenance Dosing Regimen ........................................................... 40 
1.4.3 
Rationale for Open-Label Extension Dosing Regimen ........................................... 41 
1.4.4 
Rationale for Antibiotic Pre-Treatment ................................................................... 41 
1.4.5 
Rationale for Endpoints ........................................................................................... 41 
2 
OBJECTIVES ......................................................................................................... 43 
2.1 
Primary Objective ...................................................................................................... 43 
2.2 
Key Secondary Objectives ......................................................................................... 43 
2.3 
Other Secondary Objectives ..................................................................................... 43 
2.4 
Safety Objective.......................................................................................................... 43 
2.5 
Exploratory Objectives .............................................................................................. 43 
3 
DEFINITIONS ........................................................................................................ 45 
3.1 
Clinical Remission ...................................................................................................... 45 
3.1.1 
U.S. FDA ................................................................................................................. 45
3.1.2 
EMA ........................................................................................................................ 45 
3.2 
Endoscopic Improvement .......................................................................................... 46 
3.3 
Endoscopic Remission ................................................................................................ 46 
3.3.1 
Endoscopic Remission for the Induction and Open-Label Treatment Periods ........ 46 
3.3.2 
Endoscopic Remission for the Maintenance Treatment Period (from Week 11 
through M-Week 37) ............................................................................................................ 46 
3.4 
Histological Mucosal Healing .................................................................................... 46 
3.5 
Three-Component Modified Mayo Score ................................................................ 46 
3.6 
Disease Worsening ..................................................................................................... 46 
3.7 
UC Flare ...................................................................................................................... 47 
3.8 
Engraftment ................................................................................................................ 47 
4 
STUDY DESIGN .................................................................................................... 48 
4.1 
Overview ..................................................................................................................... 48 
4.2 
Study Periods .............................................................................................................. 48 

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4.2.1 
Screening (Weeks -4 to -1; four [4] weeks) ............................................................. 48 
4.2.2 
Pre-Treatment (Week 0; six [6] days)...................................................................... 49 
4.2.3 
Induction Treatment (Week 1 – Week 11; 10 weeks) ............................................. 49 
4.2.4 
Maintenance Treatment (Week 11 – Week 37; 26 weeks) ...................................... 50 
4.2.5 
Open-Label Extension (OL-Week-0 – OL-Week-11; 11 weeks) ............................ 50 
4.2.6 
Long-Term Safety Follow-Up (26 weeks) ............................................................... 50 
5 
STUDY POPULATION ......................................................................................... 51 
5.1 
Inclusion Criteria ....................................................................................................... 51 
5.2 
Exclusion Criteria ...................................................................................................... 53 
5.3 
Subject Withdrawal and Replacement ..................................................................... 54 
5.3.1 
Reasons for Discontinuation of Treatment .............................................................. 54 
5.3.2 
Handling of Withdrawals and Discontinuation of Treatment .................................. 55 
5.4 
Termination of Study ................................................................................................. 55 
5.5 
Planned Sample Size and Number of Study Centers .............................................. 55 
5.6 
Subject Identification and Randomization .............................................................. 55 
5.6.1 
Subject Identification ............................................................................................... 55 
5.6.2 
Methods of Assigning Subjects to Study Treatment ............................................... 55 
5.6.3 
Maintaining the Randomization Codes and Breaking the Study Blind ................... 56 
6 
INVESTIGATIONAL PRODUCT ........................................................................ 58 
6.1 
SER-287 Drug Product Capsules .............................................................................. 58 
6.1.1 
Donor Screening ...................................................................................................... 58 
6.1.2 
SER-287 Manufacturing .......................................................................................... 58 
6.2 
Vancomycin HCl Hard Gelatin Capsules (“Vancomycin”) ................................... 58 
6.3 
SER-287 Placebo Capsules ........................................................................................ 58 
6.3.1 
SER-287 Placebo Manufacturing ............................................................................ 58 
6.4 
Vancomycin HCl Placebo Capsules (“Vancomycin Placebo”) .............................. 59 
6.4.1 
Vancomycin HCl Placebo Manufacturing and Storage ........................................... 59 
6.5 
Storage ........................................................................................................................ 59 
6.5.1 
SER-287 and SER-287 Placebo Storage ................................................................. 59 
6.6 
Study Drug Administration ....................................................................................... 59 
6.7 
Drug Accountability ................................................................................................... 60 
6.8 
Prior and Concomitant Medications ........................................................................ 60 
6.8.1 
Permitted Concomitant Medications ....................................................................... 60 
6.8.2 
Prohibited Concomitant Medications and Nutritional Supplements ....................... 61 
7 
VARIABLES AND METHODS OF ASSESSMENT ......................................... 62 
7.1 
Safety Variables ......................................................................................................... 62 
7.1.1 
Treatment Emergent Adverse Events ...................................................................... 63 
7.1.2 
Adverse Event of Special Interest ............................................................................ 64 
7.1.3 
Reporting Serious Adverse Events .......................................................................... 64 
7.1.4 
Follow-up of Serious Adverse Events and Adverse Events of Special Interest ...... 65 
7.1.5 
Pregnancy ................................................................................................................ 65 
7.1.6 
Laboratory Variables ............................................................................................... 66 
7.1.7 
Stool Samples .......................................................................................................... 66 
7.1.8 
Biopsy Samples ....................................................................................................... 66 
7.1.9 
Vital Signs ............................................................................................................... 67 
7.1.10 Physical Examinations ............................................................................................. 67 
7.2 
Demographics and Baseline Characteristics ........................................................... 67 
7.2.1 
Subject Demography ............................................................................................... 67 
7.2.2 
Disease History ........................................................................................................ 67 

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7.2.3 
Baseline Characteristics ........................................................................................... 68 
7.2.4 
Medical History ....................................................................................................... 68 
7.2.5 
Prior and Concomitant Medications ........................................................................ 68 
7.3 
Three-Component Modified Mayo Score ................................................................ 68 
7.3.1 
Stool Frequency Subscore ....................................................................................... 68 
7.3.2 
Rectal Bleeding Subscore ........................................................................................ 68 
7.3.3 
Endoscopic Subscore ............................................................................................... 68 
8 
STUDY CONDUCT ............................................................................................... 69 
8.1 
Study Schedule ........................................................................................................... 69 
8.2 
Procedures by Visit .................................................................................................... 69 
8.2.1 
Screening: Week -4 to -1 (Visit 1) ........................................................................... 69 
8.2.2 
Screening: Week -4 to -1:  Endoscopy Visit (Visit 2) ............................................. 70 
8.2.3 
Pre-Treatment: Week 0 (Visit 3) ............................................................................. 71 
8.2.4 
Induction Treatment: Week 1 +/-1d (Visit 4) .......................................................... 72 
8.2.5 
Induction Treatment: Week 3 +3d (Visit 5)............................................................. 72 
8.2.6 
Induction Treatment: Week 7 +3d (Visit 6)............................................................. 72 
8.2.7 
Induction Treatment: Week 11 +3d (End of Induction Treatment) (Visit 7) .......... 73 
8.2.8 
Induction Treatment: Unscheduled Visit ................................................................. 74 
8.2.9 
Maintenance Treatment: M-Week 12 +/-2d (Visit M-1) ......................................... 74 
8.2.10 Maintenance Treatment: M-Week 16 +3d (Visit M-2) ........................................... 75 
8.2.11 Maintenance Treatment: M-Week 20 +3d (Visit M-3) ........................................... 75 
8.2.12 Maintenance Treatment: M-Week 24 +3d (Visit M-4) ........................................... 75 
8.2.13 Maintenance Treatment: M-Week 28 +3d (Visit M-5) ........................................... 76 
8.2.14 Maintenance Treatment: M-Week 32 +3d (Visit M-6) ........................................... 76 
8.2.15 Maintenance Treatment: M-Week 37 +3d (Visit M-7) ........................................... 76 
8.2.16 Maintenance Treatment – Long-Term Safety Follow-Up: Phone Calls Every Four 
(4) Weeks +/-3d (Visits M-8 – M-13) .................................................................................. 77 
8.2.17 Maintenance Treatment: Unscheduled Visit ............................................................ 78 
8.2.18 Open-Label Extension: OL-Week 0 +/-2d (Visit OL-1) ......................................... 78 
8.2.19 Open-Label Extension: OL-Week 1 +/-1d (Visit OL-2) ......................................... 78 
8.2.20 Open-Label Extension: OL-Week 3 +3d (Visit OL-3) ............................................ 78 
8.2.21 Open-Label Extension: OL-Week 7 +3d (Visit OL-4) ............................................ 79 
8.2.22 Open-Label Extension: OL-Week 11 +3d (Visit OL-5) .......................................... 79 
8.2.23 Open-Label Extension – Long-Term Safety Follow-Up: Phone Calls Every Four (4) 
Weeks for 26 Weeks/EoS +/-3d (Visits OL-6 – OL-11) ...................................................... 80 
8.2.24 Open-Label Extension: Unscheduled Visit .............................................................. 80 
8.2.25 Unscheduled Visits .................................................................................................. 80 
8.2.26 End of Treatment Visit ............................................................................................ 81 
8.2.27 Handling of Withdrawals and Discontinuations of Treatment ................................ 82 
9 
STATISTICAL METHODS ................................................................................. 83 
9.1 
Study Endpoints ......................................................................................................... 83 
9.1.1 
Primary Efficacy Endpoint ...................................................................................... 83 
9.1.2 
Key Secondary Efficacy Endpoints ......................................................................... 83 
9.1.3 
Other Secondary Efficacy Endpoints ....................................................................... 83 
9.1.4 
Exploratory Efficacy Endpoints .............................................................................. 84 
9.1.5 
Safety Endpoints ...................................................................................................... 84 
9.2 
Study Subjects ............................................................................................................ 84 
9.2.1 
Disposition of Subjects ............................................................................................ 84 
9.2.2 
Protocol Deviations ................................................................................................. 84 
9.2.3 
Analysis Populations ............................................................................................... 84 

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9.3 
Multiplicity Adjustment ............................................................................................ 86 
9.4 
General Considerations ............................................................................................. 86 
9.5 
Efficacy Analyses........................................................................................................ 86 
9.5.1 
Timing of Analyses.................................................................................................. 86 
9.5.2 
Statistical Analysis and Significance Level ............................................................. 87 
9.5.3 
Missing or Spurious Data ........................................................................................ 88 
9.5.4 
Analysis of the Primary Efficacy Endpoint ............................................................. 88 
9.5.5 
Analysis of the Key Secondary Efficacy Endpoints ................................................ 88 
9.5.6 
Analyses of Other Secondary Efficacy Endpoints ................................................... 89 
9.5.7 
Analyses of Exploratory Endpoints ......................................................................... 89 
9.6 
Safety Analyses ........................................................................................................... 89 
9.6.1 
Adverse Events ........................................................................................................ 89 
9.6.2 
Clinical Laboratory Tests ........................................................................................ 90 
9.6.3 
Vital Signs ............................................................................................................... 90 
9.6.4 
Physical Examination Findings ............................................................................... 90 
9.6.5 
Pharmacokinetic Analyses ....................................................................................... 90 
9.7 
Gastrointestinal Tract Microbiome .......................................................................... 90 
9.7.1 
Microbiome Secondary Endpoint Data Analysis ..................................................... 90 
9.8 
Interim Analyses ........................................................................................................ 91 
9.9 
Determination of Sample Size ................................................................................... 91 
10 ADMINISTRATIVE REQUIREMENTS ............................................................ 92 
10.1 
Good Clinical Practice ............................................................................................... 92 
10.2 
Ethical Considerations ............................................................................................... 92 
10.3 
Subject Information and Informed Consent ........................................................... 92 
10.4 
Subject Confidentiality .............................................................................................. 93 
10.5 
Protocol Compliance .................................................................................................. 93 
10.6 
Future Use of Stored Specimens ............................................................................... 93 
10.7 
Study Monitoring ....................................................................................................... 93 
10.8 
Case Report Forms and Study Records ................................................................... 94 
10.9 
Study Completion ....................................................................................................... 95 
11 REFERENCE LIST ............................................................................................... 96 
12 APPENDICES ....................................................................................................... 101 
12.1 
Appendix 1: Mayo Score (Schroeder et al., 1987) ................................................. 101 
12.2 
Appendix 2: Stool Frequency and Rectal Bleeding Subscore Calculation 
Guidelines .............................................................................................................................. 102 
Stool Frequency Subscore .................................................................................................. 102 
Rectal Bleeding Subscore ................................................................................................... 103 
12.3 
Appendix 3: Inflammatory Bowel Disease Questionnaire (Guyatt et al., 1989) . 104 

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Protocol # SERES-201 
CONFIDENTIAL 
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Tables in Text 
Table 1: Schedule of Events: Induction Treatment .................................................. 16 
Table 2: Schedule of Events: Maintenance Treatment for Remitters ...................... 18 
Table 3: Schedule of Events: Open-Label Extension Arm for Non-Remitters ....... 20 
Table 4: SERES-101 Treatment Arms ..................................................................... 33 
Table 5: SERES-201 Induction Treatment Arms .................................................... 39 
Table 6: SERES-201 Post-Induction Treatment Arms ............................................ 40 
Table 7: Doses, Route, and Schedule of Study Drug Administration ..................... 59 
Table 8: Study Schedule .......................................................................................... 69 
Figures in Text 
Figure 1: Subject Treatment Overview: Screening Through Week 11 ..................... 14 
Figure 2: Subject Treatment Overview: Week 11 Through End-of-Study ............... 15 
Figure 3: SERES-101 Efficacy Data – ITT ............................................................... 34 
Figure 4: SERES-101 High-Confidence Engraftment of SER-287 .......................... 38 
Figure 5: SERES-201 Treatment Arms ..................................................................... 48 

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List of Abbreviations 
Abbreviation 
Term 
5-ASA
5-aminosalicylate
6-MP
6-mercaptopurine
AE 
Adverse event 
AESI 
Adverse Event of Special Interest 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
AZA 
Azathioprine 
BP 
Blood pressure 
cc 
Cubic centimeter 
CD 
Crohn’s disease 
CDER 
Center for Drug Evaluation and Research 
CFR 
Code of Federal Regulations 
CHMP 
Committee for Medicinal Products for Human Use 
Cm 
Centimeter 
CMH 
Cochran-Mantel-Haenszel 
CRO 
Contract research organization 
CRP 
C-reactive protein
CSR 
Clinical Study Report 
D 
Day 
dL 
Deciliter 
DNA 
Deoxyribonucleic acid 
eCRF 
Electronic case report form 
EIA 
Enzyme immunoassay 
EMA 
European Medicines Agency 
EDC 
Electronic data capture 
eDiary 
Electronic diary 
EOT 
End-of-treatment 
ES 
Endoscopic subscore 
FDA 
Food and Drug Administration 
FMT 
Fecal microbiota transplantation 
g 
Grams 

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GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
HCl 
Hydrogen chloride 
HDPE 
High-density polyethylene 
HR 
Heart rate 
IB 
Investigator’s Brochure 
IBD 
Inflammatory bowel disease 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug Application 
IP 
Investigational product 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat; Intention-to-Treat 
IXRS 
Interactive web/voice response system 
JAK 
Janus kinase 
LFT 
Liver function test 
LOCF 
Last observation carried forward 
mcITT 
Microbiome Modified Intent-to-Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
MH 
Medical history 
mITT 
Modified Intent-to-Treat 
mL 
Milliliter 
mm3 
Cubic millimeter 
mmHg 
Millimeters of mercury 
MMX 
Multi-matrix system 
Pbo 
Placebo 
PE 
Physical examination 
PGA 
Physician Global Assessment 
PI 
Principal Investigator 
PP 
Per Protocol 
PT 
Preferred term 
QD 
Once-daily 

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1.1.3 Disease Pathogenesis and Microbiome Involvement 
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). 
The microbiomes of adults are comprised of four (4) principal bacterial phyla: 
Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria, of which Bacteroidetes and 
Firmicutes are the dominant members in healthy subjects (Human Microbiome Project 
Consortium, 2012).  Inflammatory bowel disease (IBD), including UC, is widely thought 
to be linked to the gut microbiome, and, in turn, to environmental factors which affect 
microbiome composition (Huttenhower et al., 2014).  Multiple cohort studies have 
characterized changes in fecal and mucosal microbiomes associated with UC using next 
generation sequencing methods including 16S rRNA and whole metagenomic shotgun 
sequencing (WMS) (Frank et al., 2007; Morgan et al., 2012; Papa et al., 2012; Walujkar 
et al., 2014; Willing et al., 2010; Wills et al., 2014, Halfvarson et al., 2017, Schirmer et 
al., 2018).   
The emerging picture from these studies is that the microbiome of UC patients tends to 
exhibit certain general features of dysbiosis, including: (1) lower microbial diversity, 
(2) a greater prevalence of facultative anaerobes in the family Enterobacteriaceae, and
(3) a depletion of commensal spore-forming taxa in 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).  Importantly, however,
multiple studies have identified substantial variability in UC microbiomes related to
disease subtype and disease severity (Morgan et al., 2012; Papa et al., 2012, Halfverson
et al., 2017; Schirmer et al., 2018).  Studies focusing primarily on UC subjects in clinical
remission, or with mild forms of disease, find little differentiation between microbiomes
from UC subjects and those from healthy individuals (Willing et al., 2010), and other
studies have found a clear connection between increased disease severity and increased
dysbiosis (Papa et al., 2012; Walujkar et al., 2014).  A meta-analysis of four (4) cohort
studies (Morgan et al., 2012; Papa et al., 2012; Willing et al., 2010; Wills et al., 2014),
conducted by Seres, supports the above general conclusions from the literature.
Comparison of bacterial richness (α-diversity) and composition (β-diversity) of
microbiomes from UC subjects to 313 healthy individuals characterized with 16S rRNA
sequencing (The Human Microbiome Project Consortium, 2012) showed that UC
subjects with active disease tended to have less diverse microbiomes than individuals
with inactive disease, and that UC subject microbiomes were significantly enriched in
genera from the family Enterobacteriaceae, which have been implicated in several
studies as related to increased oxidative stress and host inflammatory response (Winter et
al., 2013; Caballero and Pamer, 2015; Morgan et al., 2012; Lawley and Walker, 2013).

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compared to placebo or the SER-287 weekly treatment arms.  This finding provides an 
independent assessment of efficacy as the GI AEs likely reflect ulcerative colitis disease 
activity. 
1.2.3 Baseline Microbiome Composition 
Comparison of the baseline microbiome of UC subjects enrolled in the SERES-101 
Phase 1B study to 202 healthy individuals characterized as part of the Human 
Microbiome Project (Lloyd-Price et al., 2017), based on high-resolution WMS genomics, 
demonstrates features of UC dysbiosis comparable to that reported in the literature.   
First, minimal differences in total diversity were observed between UC and healthy 
subjects; this is similar to findings in recent large cohort studies of the UC microbiome 
(Imhann et al., 2018, Halfverson et al., 2017, Schirmer et al., 2018).  Notably, since the 
SERES-101 subject population consists of subjects with mild-to-moderate disease, the 
expected baseline dysbiosis is less than observed in cohort studies which include subjects 
with severe disease.  Second, microbiomes from SERES-101 subjects at baseline tended 
to have a higher abundance of taxa from the family Enterobacteriaceae than healthy 
subjects (p=0.110, 2-tailed t-test), consistent with the findings of a meta-analysis of 
cohort studies conducted by Seres.  Additionally, the mean abundance of 
Enterobacteriaceae was higher in subjects with more severe disease at baseline (baseline 
endoscopic subscore [ES] ≥ 2), with the highest abundance in subjects with baseline ES 
of 3.  The mean abundance of Enterobacteriaceae was 2.2-fold higher in subjects with 
baseline ES of 3 than in subjects with baseline ES of 1.  Notably, several publications 
implicate an increased abundance of Enterobacteriaceae taxa with increased oxidative 
stress in the gastrointestinal tract, related to increased host inflammatory response 
(Winter et al., 2013; Caballero and Pamer, 2015; Morgan et al., 2012; Lawley and 
Walker, 2013). 
1.2.4 Microbiome Engraftment and Post-Baseline Composition 
The two microbiome primary objectives of the SERES-101 study were to (1) determine 
the engraftment of SER-287 bacteria into each of the treatment arms, relative to placebo, 
and (2) to compare the baseline composition of the intestinal microbiome to the post-
baseline composition after treatment with SER-287, or placebo.  The fecal microbiome of 
SERES-101 subjects and SER-287 drug product were characterized using WMS, a high-
resolution and widely utilized methodology (e.g. Lloyd-Price et al., 2017) which enables 
species-level taxonomic identifications (Truong et al., 2015).   
A statistically significant signal of engraftment of SER-287 bacteria in SERES-101 
subjects was observed following treatment with SER-287, which led to a rapid and 
durable change in subject microbiomes (Figure 4).  Vancomycin pre-treatment was 
associated with significantly higher levels of engraftment of SER-287 relative to placebo 
pre-treatment in subjects receiving a weekly dose of SER-287, starting at one (1) week 
after the start of dosing (p<0.007 for Vanco/SER287 Daily vs. Pbo/Pbo Daily, p<0.018 
for Vanco/SER287 Wkly vs. Pbo/Pbo Daily, one-sided Mann-Whitney U test).  
Engraftment was dose-dependent within vancomycin pre-treatment arms; the daily 
dosing arm showed significantly faster engraftment than the weekly dosing arm (p<0.012 
for Vanco/SER287 Wkly vs. Vanco/SER287 Daily).  Significant engraftment of 

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SER-287 in the vancomycin pre-treatment arms was observed as early as one (1) week 
after the initial SER-287 dose (p=0.004 for Vanco/SER287 Daily vs. Pbo/Pbo Daily, 
p=0.025 for Vanco/SER287 Wkly vs. Pbo/Pbo Daily).  Additionally, engraftment of 
SER-287 bacteria in the vancomycin pre-treatment arms was detectable four (4) weeks 
after the completion of SER-287 dosing (p=0.005 for Vanco/SER287 Daily vs. Pbo/Pbo 
Daily, p=0.007 for Vanco/SER287 Wkly vs. Pbo/Pbo Daily), at levels comparable to 
those observed during the dosing period, suggesting that SER-287 taxa can durably 
persist in subjects for at least four (4) weeks following cessation of drug administration 
(Figure 4). 
Treatment with SER-287 led to changes in the overall composition of the microbiome.  
The microbiome of subjects in the Vanco/SER-287 Daily dosing arm shifted and 
exhibited significantly greater similarity to SER-287 drug product one (1) week after the 
start of treatment (p=0.001); subjects in the SER-287 weekly dosing arm shifted, but did 
not show comparable similarity to the SER-287 dose until the study endpoint (p=0.016) 
(Figure 4).   
Notably, the composition of the microbiome in subjects in the daily dosing arm was 
stable from one (1) week after the start of treatment through four (4) weeks after the end 
of the dosing period.  Subjects in the daily dosing arm also showed significantly higher 
richness of spore-forming taxa at the end of the treatment period (p=0.037) relative to 
baseline, indicating that treatment with SER-287 was effective in shifting the 
composition of subject microbiomes.  Notably, comparison of the microbiomes from 
subjects who achieved clinical remission in the Vanco/SER-287 Daily arm to those who 
did not, revealed distinct patterns in microbial composition – subjects who achieved 
remission tended to demonstrate an increased prevalence of certain commensal species, 
including both species present and absent in SER-287 (Figure 4). 

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efficacy endpoints in this study include clinical remission (primary), endoscopic 
remission and endoscopic improvement (secondary).  In this study, clinical remission is 
based on the Three-Component Modified Mayo Scoring system and is defined as a stool 
frequency subscore of 0 or 1 with at least a one-point decrease from baseline, rectal 
bleeding subscore of 0 and endoscopic subscore of 0 or 1 (modified, excludes friability), 
with at least a one-point decrease from baseline.  All endpoints will be measured at 
1) baseline (Screening Visit 2) prior to randomization, 2) after 10 weeks of induction
treatment and 3) after Maintenance or Open-Label treatment.
Symptoms of disease will be assessed throughout the study via the patient reported 
outcome components of the Mayo score, rectal bleeding and stool frequency, using daily 
data from subjects’ electronic diary (eDiary) entries.   
Drug effects on mucosal healing will be assessed using lower endoscopy and histologic 
assessment of biopsies:  
1. Appearance of the mucosa will be assessed using lower endoscopy and the Mayo
scoring system
2. Histological mucosal healing will be assessed using Robarts Histopathological
Index (RHI; Mosli et al., 2017) and Geboes Score (Geboes et al., 2000)
Safety and tolerability will be evaluated by comparing safety parameters across treatment 
arms, including incidence of AEs, laboratory evaluations, vital sign measurements and 
physical examination findings, before and after treatment. 
SERES-101 provided safety on 47 subjects who received up to eight (8) weekly doses 
(32 subjects) or up to 56 daily doses (15 subjects) of SER-287.  The current study will 
add safety data for 67 subjects at approximately the same dose as the SERES-101 study 
(Arm B, Table 5), and for 67 subjects at a lower dose (Arm C, Table 5). 
This study will also evaluate microbiome changes.  Engraftment (a secondary endpoint) 
is defined as the outgrowth of bacteria that comprise the SER-287 drug product in a 
subject’s gastrointestinal tract, post-treatment.  This study will evaluate the engraftment 
of SER-287 bacteria in each treatment arm and will evaluate mechanism of action data 
for SER-287.  
There are several additional exploratory endpoints. 

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2 
OBJECTIVES 
2.1 
Primary Objective 
•
To demonstrate the efficacy of SER-287, after 10 weeks of induction dosing
(following vancomycin pre-treatment), in achieving clinical remission
2.2 
 Key Secondary Objectives 
•
To demonstrate the efficacy of SER-287, after 10 weeks of step-down induction
dosing (following vancomycin pre-treatment), in achieving clinical remission
•
To demonstrate the efficacy of SER-287, after 10 weeks of induction dosing
(following vancomycin pre-treatment), in achieving endoscopic improvement
•
To demonstrate the efficacy of SER-287, after 10 weeks of step-down induction
dosing (following vancomycin pre-treatment), in achieving endoscopic improvement
2.3 
Other Secondary Objectives 
•
To demonstrate the efficacy of each SER-287 treatment arm in achieving endoscopic
remission after 10 weeks of induction treatment
•
To demonstrate the efficacy of each SER-287 treatment arm in achieving histological
mucosal healing after 10 weeks of induction treatment
•
To demonstrate the efficacy of each SER-287 treatment arm in achieving clinical
remission with normalization of stool frequency after 10 weeks of induction
treatment
•
To evaluate the efficacy of each SER-287 treatment arm on symptomatic remission
(rectal bleeding and stool frequency) after 10 weeks of induction treatment
•
To evaluate the engraftment of SER-287 bacteria from each SER-287 treatment arm
into the intestinal microbial community over time
•
For EMA consideration only (see Section 3, Definitions):
o
To demonstrate the efficacy of SER-287 to induce clinical remission, using
less stringent definition
o
To demonstrate the efficacy of SER-287 to induce clinical remission, using
more stringent definition
o
To demonstrate the efficacy of SER-287 to induce symptomatic remission
and endoscopic remission as co-endpoints
2.4 
Safety Objective 
To evaluate safety and tolerability of SER-287 
2.5 
Exploratory Objectives 
•
To evaluate clinical remission at the end of maintenance treatment
•
To evaluate endoscopic remission at the end of maintenance treatment
•
To evaluate histological mucosal healing at the end of maintenance treatment
•
To evaluate clinical remission at the end of open-label treatment
•
To evaluate endoscopic improvement at the end of open-label treatment

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•
To evaluate endoscopic remission at the end of open-label treatment
•
To evaluate histological mucosal healing at the end of open-label treatment
•
To evaluate the effect of SER-287 treatment on symptomatic remission (rectal
bleeding and stool frequency) over time
•
To evaluate the clinical remission rate of SER-287, by donor, after 10 weeks of
induction treatment
•
To assess improvement in quality of life, as measured by the Inflammatory Bowel
Disease Questionnaire (IBDQ)
•
To assess changes in serum biomarkers (C-reactive protein [CRP]) and fecal
biomarkers (fecal calprotectin)
•
To evaluate changes in the composition of the intestinal microbiome over time
•
To evaluate changes in signatures of host and microbial functional responses over
time

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3 
DEFINITIONS 
3.1 
Clinical Remission 
Due to the differences in the definition of clinical remission in the U.S. FDA Guidance 
Ulcerative Colitis: Clinical Trial Endpoints (FDA CDER 2016) and the EMA “Guideline 
on the development of new medicinal products for the treatment of Ulcerative Colitis” 
(EMA/CHMP, 2018), the definitions for clinical remission, as well as associated 
endpoints, to be used for the U.S. FDA and the EMA analyses, are provided below. 
3.1.1 U.S. FDA
3.1.1.1 Clinical Remission for the Induction and Open-Label Treatment Periods: 
•
Stool Frequency subscore = 0 or 1, with at least one-point decrease from baseline
•
Rectal Bleeding subscore = 0
•
Endoscopic subscore = 0 or 1 on modified Mayo Score, with at least one-point
decrease from baseline
•
No occurrence of UC Flare during the treatment period
3.1.1.2 Clinical Remission for the Maintenance Treatment Period (Sustained from 
Week 11 through M-Week 37): 
•
Stool Frequency subscore = 0 or 1
•
Rectal Bleeding subscore = 0
•
Endoscopic subscore = 0 or 1 on modified Mayo Score
•
No occurrence of UC Flare during the treatment periods
3.1.1.3 Clinical Remission including normalization of stool frequency: 
•
Stool Frequency subscore = 0
•
Rectal Bleeding subscore = 0
•
Endoscopic subscore = 0 or 1 on modified Mayo Score, with at least one-point
decrease from baseline
•
No occurrence of UC Flare during the treatment period
3.1.2 EMA 
3.1.2.1 Clinical Remission – Less stringent: 
•
Stool Frequency subscore = 0 or 1
•
Rectal Bleeding subscore = 0
•
Endoscopic subscore = 0 or 1 on modified Mayo Score, with at least one-point
decrease from baseline
•
No occurrence of UC Flare during the treatment period
3.1.2.2 Clinical Remission – More stringent: 
•
Stool Frequency subscore = 0 or 1
•
Rectal Bleeding subscore = 0

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•
Endoscopic subscore = 0 on modified Mayo Score
•
No occurrence of UC Flare during the treatment period
3.1.2.3 Co-endpoints: 
•
Symptomatic remission:
a.
Stool Frequency subscore = 0 or 1
b. Rectal Bleeding subscore = 0
•
Endoscopic remission
a.
Endoscopic subscore = 0 or 1 on modified Mayo Score, with at least one-
point decrease from baseline
3.2 
Endoscopic Improvement 
Endoscopic subscore decrease from baseline of at least one (1) point, as assessed by 
flexible sigmoidoscopy or colonoscopy 
3.3 
Endoscopic Remission 
3.3.1 Endoscopic Remission for the Induction and Open-Label Treatment Periods 
Endoscopic subscore = 0 or 1 on modified Mayo Score, with at least one (1) point 
decrease from baseline, as assessed by flexible sigmoidoscopy or colonoscopy 
3.3.2 Endoscopic Remission for the Maintenance Treatment Period (from Week 11 
through M-Week 37) 
Endoscopic subscore = 0 or 1 on modified Mayo Score, as assessed by flexible 
sigmoidoscopy or colonoscopy 
3.4 
Histological Mucosal Healing 
Statistically significant decrease from baseline, using the Robarts Histopathological 
Index (RHI) scoring system 
3.5 
Three-Component Modified Mayo Score 
Sum of the below three (3) subscores: 
1. Endoscopic subscore
2. Stool frequency subscore
3. Rectal bleeding subscore
3.6 
Disease Worsening 
An increase by two (2) or more points, on two (2) days within a three (3) day period, of 
the patient reported outcomes (stool frequency and rectal bleeding) of the modified Mayo 
score, 
•
Compared to baseline score (Visit 2) if disease worsening is during the Induction
Treatment period, or

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•
Compared to the post-10-week induction treatment score if disease worsening is
after the Induction Treatment period
3.7 
UC Flare 
UC symptom changes (which may include disease worsening, as defined above), as 
determined by the principal investigator to be significant enough to warrant addition of a 
new UC medication, an increase in dose of a baseline UC medication, or surgery 
3.8 
Engraftment 
Outgrowth of bacteria that comprise the SER-287 drug product in a subject’s 
gastrointestinal tract, post-treatment 

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5 
STUDY POPULATION 
Subjects must meet all the inclusion criteria and none of the exclusion criteria. 
5.1 
Inclusion Criteria 
To be eligible for enrollment, a subject must meet all the following criteria before 
undergoing any study-related procedures: 
1. Signed informed consent prior to initiation of any study-specific procedure or
treatment.  The subject must be willing to provide written informed consent and
understand the potential risks and benefits from study enrollment and treatment.
The subject must also be willing and able to comply with the scheduled visits,
treatment plan, laboratory tests, daily eDiary and other study procedures.
2. Male or female (non-lactating), 18-80 years of age, inclusive
3. Documented diagnosis of ulcerative colitis at least three (3) months prior to
Screening.  Documentation should include lower endoscopic (flexible
sigmoidoscopy or colonoscopy) evidence or histological evidence (biopsy report)
of UC; however, UC medical treatment records may be sufficient, as determined
by the PI.  Subjects must also have a minimum disease extent of 15 cm from the
anal verge, as determined at the Screening endoscopy.
4. Active mild-to-moderate UC as determined by a Three-Component Modified
Mayo Score of 3 to 7, inclusive, composed of endoscopic subscore (≥ 1, as
determined by local and central reader scores, with adjudication by a second
central reader, if necessary), stool frequency subscore (≥ 1) and rectal bleeding
subscore (no eligibility requirement).  There will be a maximum time of seven (7)
business days between the Screening endoscopy and randomization.
5. Subjects must be willing to undergo a lower endoscopy (flexible sigmoidoscopy
or colonoscopy), including biopsy sample collection, at all specified timepoints.
6. Subjects with an inadequate response to, loss of response to, or intolerance of, at
least one (1) of the following conventional therapies: 5-ASA compounds,
corticosteroids, 6-mercaptopurine (6-MP) or azathioprine (AZA), anti-TNFα,
anti-integrin or tofacitinib (note full definition later within Section 5.1)
7. If female, is either:
a.
Not of childbearing potential, defined as postmenopausal (≥ 12 continuous
months of amenorrhea with no other cause than menopause) or surgically
sterile due to bilateral tubal ligation, bilateral oophorectomy, or
hysterectomy
b. Of childbearing potential and participates in any activity associated with
risk of pregnancy: is practicing at least one (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 one (1) of the above methods for the duration of the
study.
8. If male and partner is of childbearing potential, subject agrees to practice at least
one (1) highly effective method of birth control for the duration of the study.

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Note definition for Inclusion Criterion #6:  Subjects who have demonstrated, over the 
previous five (5) year period, an inadequate response to, loss of response to, or 
intolerance of, at least one (1) of the following agents, as defined below: 
•
5-ASA compounds:
o
Signs and symptoms of persistently active disease despite taking a 
therapeutic dose of a 5-ASA compound (based on the product label for 
each compound, per PI judgement) for a minimum of four (4) weeks, or
o
History of intolerance to at least one (1) 5-ASA (discontinuation due to 
side effects)
•
Corticosteroids:
o
Signs and symptoms of persistently active disease despite a history of at 
least one (1) four-week induction regimen that included a dose equivalent 
to prednisone ≥ 30 mg or budesonide ≥ 9 mg daily, orally for at least two
(2) weeks, or intravenously for at least one (1) week, or
o
Two (2) failed attempts to taper corticosteroids to below a dose equivalent 
to prednisone 10 mg daily, orally, on two (2) separate occasions, or
o
History of intolerance of corticosteroids (including, but not limited to 
Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, or 
neuropsychiatric side-effects, including insomnia, associated with 
corticosteroid treatment)
•
Immunomodulators:
o
Signs and/or symptoms of persistently active disease despite at least three
(3) months of treatment with one (1) of the following:

oral AZA (≥ 1.5 mg/kg/day) or 6-MP (≥ 0.75 mg/kg/day), or

oral AZA or 6-MP within a therapeutic range, as judged by 
thioguanine metabolite testing, or

a combination of a thiopurine and allopurinol within a therapeutic 
range, as judged by thioguanine metabolite testing, or

history of intolerance to at least one (1) immunomodulator
(including but not limited to nausea/vomiting, abdominal pain, 
pancreatitis, liver function test abnormalities and lymphopenia)
•
Pathway specific drugs for UC treatment, including anti-TNF antibodies, anti-
integrin antibodies, or janus kinase (JAK) inhibitors (such as tofacitinib):
o
Signs and symptoms of persistently active disease despite induction 
treatment at the approved induction dosing that was indicated in the 
product label at the time of use, or
o
Loss of response: Recurrence of signs and symptoms of active disease 
during approved maintenance dosing following prior clinical benefit
(discontinuation despite clinical benefit does not qualify as having failed 
or being intolerant to UC biologic therapy), or

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o
Intolerance: History of intolerance to infliximab, adalimumab,
golimumab, vedolizumab, tofacitinib or other approved biologics or JAK
inhibitors (including but not limited to infusion-related event,
demyelination, congestive heart failure, serious infection, or any other
drug-related AE that led to a reduction in dose or discontinuation of the
medication).
5.2 
Exclusion Criteria 
A subject will not be enrolled if the subject meets any of the following criteria: 
1. Known history of Crohn’s disease
2. No previous history of treatment for UC (treatment-naïve subjects should not be
enrolled)
3. Subjects on steroid medication (e.g. prednisone, budesonide, budesonide
MMX®) who are unable to have steroids tapered, and be completely off steroids
at least two (2) weeks prior to Screening
4. Subjects who have received any investigational or approved biologic therapy (e.g.
infliximab, adalimumab, golimumab, certolizumab, vedolizumab, ustekinumab,
natalizumab) within eight (8) weeks prior to Screening or five (5) half-lives prior
to Screening (whichever is longer)
5. Subjects who have received any investigational or approved non-biologic therapy
(e.g. cyclosporine, tacrolimus, thalidomide, methotrexate, tofacitinib), except for
those specifically listed in the Permitted Concomitant Medications (e.g. stable
dose of 6-mercaptopurine, azathioprine, methotrexate for ≥ 12 weeks prior to
Screening), for the treatment of underlying disease, within 30 days or five (5)
half-lives prior to Screening (whichever is longer)
6. Major gastrointestinal surgery (not including appendectomy or cholecystectomy)
within two (2) months before Screening, or any history of total colectomy
7. Subjects with active celiac disease (i.e., active diarrhea due to documented celiac
disease)
8. Subjects with evidence of, or treatment for, Clostridium difficile infection, or
other intestinal pathogen, within 30 days prior to Screening
9. Subjects with Clostridium difficile positive stool, performed with a toxin enzyme
immunoassay (EIA) by the Central Laboratory.  Subjects who test positive for C.
difficile can be treated with standard of care antibiotics and rescreened for the
study after 30 days, as per Exclusion Criterion #8.
10. Oral antibiotic use within 30 days before Screening
11. Expected to receive antibiotics (i.e., for planned/anticipated procedure) within the
Induction Treatment period
12. Received an investigational drug or live vaccine within two (2) months before
Screening
13. Previously enrolled in a Seres Therapeutics SER-109 or SER-287 study
14. Received a fecal microbiota transplant (FMT; includes human microbiota-based
therapeutics) within three (3) months prior to Screening
15. 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:

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a.
Known hypogammaglobulinemia
b. Known severe immunodeficiency
c.
Underlying liver function test (LFT) [Screening alanine aminotransferase
(ALT) or aspartate aminotransferase (AST)] abnormalities greater than 3x
upper limit of normal (ULN)
d. Absolute neutrophil count (ANC) < 500 cells/mm3
e.
Hemoglobin levels < 9 g/dL
16. Subjects with anatomic or medical contraindications to lower endoscopy (flexible
sigmoidoscopy or colonoscopy), including but not necessarily limited to toxic
megacolon, gastrointestinal 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)
17. Unable to stop steroid enemas or suppositories, or 5-ASA enemas or
suppositories, at least two (2) weeks prior to Screening
18. Unable to stop probiotic treatment at least one (1) week prior to Screening.  Note:
food containing probiotics are permitted.
19. Known active malignancy, except for basal cell skin cancer or squamous cell skin
cancer, or concurrent intensive induction chemotherapy, radiotherapy, or biologic
treatment for active malignancy (subjects on maintenance chemotherapy may
only be enrolled after consultation with medical monitor)
20. Unable to comply with the protocol requirements, including the ability to take
oral drugs; or any condition that, in the opinion of the investigator, might
interfere with study objectives or compromise patient safety, including if the
subject is likely to require surgery for UC during the study period
21. Known allergy or intolerance to oral vancomycin
22. Current or recent history (six [6] months prior to Screening) of drug or alcohol
abuse
5.3 
Subject Withdrawal and Replacement 
5.3.1 Reasons for Discontinuation of Treatment 
A subject may discontinue treatment after discussion with the investigator and/or medical 
monitor for the following reasons: 
•
Pregnancy (see Section 7.1.5, Pregnancy)
•
Adverse event(s)
•
At the discretion of the Investigator
•
Subject choice (withdrawal of consent by subject; investigator will attempt to
ascertain reason)
•
Protocol violation
•
Non-compliance with study drug
•
Non-compliance with eDiary entries

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Subjects should continue to be followed for safety assessments up to 26 weeks after last 
study drug dose.  However, a subject may withdraw from the study at any time for any 
reason, without any consequence.  
5.3.2 Handling of Withdrawals and Discontinuation of Treatment 
Subjects who discontinue from treatment early will enter the long-term safety follow-up 
period.  The primary reason for discontinuation of treatment will be recorded in the 
subject’s clinical records and in the electronic data capture (EDC) system.  If a subject 
discontinues treatment, the Investigator must make every effort to perform the End of 
Treatment Visit, as described in Section 8.2.26, End of Treatment Visit. 
Subjects who withdraw from the study will have the reason for withdrawal documented 
in the EDC system.  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, three [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). 
5.4 
Termination of Study 
Although the Sponsor has every intention of completing the study, the Sponsor may 
terminate the study at any time for clinical or administrative reasons. 
5.5 
Planned Sample Size and Number of Study Centers 
Approximately 201 subjects will be enrolled at approximately 104 sites in North 
America.  
5.6 
Subject Identification and Randomization 
5.6.1 Subject Identification 
All screened subjects will be assigned a unique subject identification (SID) number that 
will be used through Screening, Pre-Treatment, Treatment and Follow-Up periods.  
5.6.2 Methods of Assigning Subjects 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 Week 0 (Visit 3), after all screening procedures 
have been performed and eligibility for the study is confirmed.  Subjects will be 

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randomized via the IXRS to one (1) of the three (3) study arms (Figure 5).  
Randomization will be stratified by subjects’ baseline endoscopic subscore (1-2 vs. 3) 
and by subjects’ concomitant use of UC medications at baseline (5-ASA alone vs. 
immunomodulators with or without 5-ASA vs. none).  An adaptive subject 
randomization algorithm will be employed to facilitate balance among the different 
donors within each of the SER-287 arms. 
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, the following people will remain blinded to the treatment 
assignment: subjects, investigators, other study site personnel, clinical staff, medical 
monitor, study site monitors and other sponsor representatives involved in the clinical 
aspects of study conduct.  
5.6.3 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 personnel who require 
knowledge of treatment assignments will be unblinded [e.g., staff involved in serious 
adverse event 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 
regulatory reporting purposes. 
If the blind is broken, the date, time, and reason must be recorded in the EDC system and 
any associated SAE 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 (Week 0 
[Visit 3] to Week 11 [Visit 7]) data is declared complete and final, the study blind codes 
will be broken for the induction period efficacy analyses.  The Maintenance Treatment 
period will remain blinded until all data collected through M-Week 37 (Visit M-7) has 
been entered, cleaned and declared complete and final.  Only limited study personnel will 

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have the access to the treatment code.  The remaining study team personnel (majority), 
PIs and subjects will remain blinded until the study is completed. 

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6.8.2 Prohibited Concomitant Medications and Nutritional Supplements 
The following prohibited concomitant medications and nutritional supplements may not 
be administered at any time through the study period.  Subjects who initiate the following 
treatments will be discontinued from further study drug administration. 
•
Oral, intravenous (IV) and rectal steroids (e.g. prednisone, budesonide,
budesonide MMX®)
•
5-ASA enemas or suppositories
•
Any investigational or approved biologic therapy (e.g. infliximab, adalimumab,
golimumab, certolizumab, vedolizumab, ustekinumab, natalizumab)
•
Any investigational or approved non-biologic therapy (e.g. cyclosporine,
tacrolimus, thalidomide, methotrexate, tofacitinib)
•
Anti-diarrheals (e.g. loperamide, diphenoxylate/atropine, or bile-salt sequestrant
[cholestyramine, colesevelam])
•
Probiotics (food containing probiotics are permitted)
•
Use of any nutritional supplement which claims to support or promote gut health
should be determined by medical monitor.

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7 
VARIABLES AND METHODS OF ASSESSMENT 
7.1 
Safety Variables 
Safety evaluations include medical history, assessment of AEs, clinical laboratory tests 
(chemistry, hematology and urinalysis), physical examination and vital signs.  
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 one (1) of the 
criteria above will not be reported as AEs.  Repeating a test because of an abnormal 
result, in the 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.

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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. 
The Investigator is responsible for: 
•
Informing the sponsor if a subject or a subject’s partner becomes pregnant during the
study.  A “Pregnancy Report Form” will be generated, and the pregnancy will be
documented in the safety database and outcome of the pregnancy will be
documented.
•
Evaluating subject safety including assessment of AEs for seriousness, severity, and
causality.
•
Informing the IRB/IEC of AEs as required, and SAEs as per IRB/IEC guidelines.
7.1.1 Treatment Emergent Adverse Events 
Collection of adverse events will begin following the first administration of study pre-
treatment medication on Week 0 (Visit 3) and will be collected through the first four (4) 
weeks of the Long-Term Safety Follow-Up Period. 
An adverse event 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 it is related to the study drug, or not.   
A serious adverse event 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 inpatient 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).
•
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.

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If a female partner of a male study subject who has been exposed to the study drug 
becomes pregnant, the outcome of the pregnancy should be documented. 
7.1.6 Laboratory Variables 
All hematology and blood chemistry laboratory tests will be performed by the central 
laboratory.  The laboratory facilities for analysis of clinical laboratory samples obtained 
under this protocol will have adequate licensure and accreditation.  Urine pregnancy tests 
will be performed at the sites.  Details of sample handling, specific tests performed, and 
methodology will be provided in the laboratory manual. 
Blood samples for hematology, blood chemistry, and biomedical research will be 
obtained according to the Schedule of Events (Table 1, Table 2, Table 3).  Blood samples 
for hematology and blood chemistry obtained on Day 1 (pre-dose) will be used to 
determine baseline data but will not be used to confirm eligibility criteria. 
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 the value is 
of clinical significance and should be recorded as an AE.  Actual laboratory results will 
not be captured within the EDC system.  However, if any laboratory results meet the 
reporting requirements for an AE, the event term (e.g., elevated transaminase) will be 
recorded within the EDC system as an AE or SAE, as applicable. 
7.1.7 Stool Samples 
Stool samples will be collected by the subjects, as detailed in Section 8, Study Conduct.  
Stool sample collection, handling, storage and processing procedures will be defined in 
stool sample manuals for sites and study subjects.  When lower endoscopies are being 
performed, stool samples will be collected prior to the start of the clear liquid diet, in 
preparation for endoscopy.   
7.1.8 Biopsy Samples 
Four (4) biopsies will be obtained from the area of worst disease, with a minimum 
disease extent of 15 cm from the anal verge, before and after treatment, as detailed in 
Section 8, Study Conduct.  The biopsies collected after treatment will be from the same 
location as those collected before treatment.  Three (3) of the four (4) biopsy samples per 
visit will be placed in formalin, for histopathology, and one (1) will be placed in 
RNALater, for mucosal genomic analyses.  Samples will be processed at the clinical site, 
and then shipped to the central laboratory, according to the procedures defined in the 
endoscopy and histopathology charters.  Refer to the endoscopy and histopathology 
charters for full details. 

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7.1.9 Vital Signs 
The following vital signs will be assessed in accordance with the Schedule of Events 
(Table 1, Table 2, Table 3): 
•
Blood pressure (BP; systolic and diastolic; mmHg)
•
Heart rate (HR; beats per minute)
•
Body temperature (°C)
•
Respiration rate (breaths per minute)
The Investigator or designee will indicate whether a value is of clinical significance and 
should be recorded as an AE.   
7.1.10 Physical Examinations 
The physical examination includes an assessment of general appearance and evaluation 
of the following: Head/Eyes/Ears/Nose/Throat; Neck; Lungs and Heart; Abdomen; 
Lymph Nodes; Extremities; Neurological; Other. 
Abnormal clinically significant findings will be reported as medical history or AEs, as 
determined by the Investigator. 
7.2 
Demographics and Baseline Characteristics 
Demographics and Baseline Characteristics consist of those variables that are assessed 
only at Screening/baseline. 
7.2.1 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)
7.2.2 Disease History 
•
UC history

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7.2.3 Baseline Characteristics 
•
General medical history
•
General surgical history
•
Smoking history
7.2.4 Medical History 
Any previous and concomitant diseases before Screening will be documented as medical 
history.  Medical history will be obtained by interviewing the subject and by inspecting 
his/her medical records. 
7.2.5 Prior and Concomitant Medications 
Prior and concomitant medication will be documented as described in Section 6.8, Prior 
and Concomitant Medications.  Prior and concomitant medications will be coded using 
the World Health Organization (WHO) Drug Dictionary.  Prior UC medications are of 
particular interest, as well as reason for stoppage – lack of efficacy or intolerance. 
7.3 
Three-Component Modified Mayo Score 
To be eligible for enrollment, a subject must have active mild-to-moderate UC as 
determined by a Three-Component Modified Mayo Score of 3 to 7, inclusive.  The total 
Three-Component Modified Mayo Score is the sum of the below three (3) subscores, 
which will be calculated electronically from subject eDiary entries and central endoscopy 
reads. 
7.3.1 Stool Frequency Subscore 
To be eligible for enrollment, a subject must have a stool frequency subscore ≥ 1.  Stool 
frequency will be recorded daily by enrolled subjects using an eDiary.  Subscore 
calculation guidelines can be found in Appendix 2. 
7.3.2 Rectal Bleeding Subscore 
There is no rectal bleeding subscore requirement for enrollment.  Rectal bleeding will be 
recorded daily by enrolled subjects using an eDiary.  Subscore calculation guidelines can 
be found in Appendix 2. 
7.3.3 Endoscopic Subscore 
To be eligible for enrollment, a subject must have an endoscopic subscore ≥ 1.  
Endoscopic subscores will be determined by qualified gastroenterologists – first locally, 
and then by an independent, blinded central reader.  If the scores are discordant, a second 
independent, blinded central reader will score the image (adjudication).  If all of the 
scores are different from one another, then the median of the three (3) scores will be used 
as the final endoscopic subscore.  
If the endoscopic subscore is missing, the subject will be assigned an outcome of failure 
for all endpoints which are derived using the endoscopic subscore. 

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•
Perform full physical exam
•
Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory
rate, temperature)
•
Obtain height and weight
•
Collect blood, urine and stool samples and ship to the central laboratory for
evaluation of:
o
Blood chemistry
o
Hematology
o
Serum pregnancy test for women of childbearing potential (WOCBP)
o
Blood & Serum for Future Biomedical Research
o
Urinalysis:  Urine dipstick performed at the study site; if positive for nitrates
and/or leukocytes, send sample to central laboratory for analysis
•
Subject should be asked to provide a stool sample on site, if possible, to be used
for Clostridum difficile testing (toxin enzyme immunoassay [EIA]), microbiome
and metabolomics.  If unable to produce a stool sample on site, subject should be
provided with a stool collection kit to take home.  Stool collection done at home
should be returned the next day by the subject or can be returned to the clinic via
courier.
•
Fecal calprotectin
•
Obtain history of stool frequency and rectal bleeding
•
Review subject eDiary Instructions with subject for recording of daily rectal
bleeding & stool frequency
•
Review stool collection handling and storage instructions with subject
•
Provide stool collection kit to subject for next clinic visit
•
Subject eDiary (daily rectal bleeding, stool frequency)
Note: A minimum of seven (7) days between Visit 1 and Visit 2 are required to 
ensure there are a sufficient quantity of daily eDiary entries to calculate the Stool 
Frequency subscore.  The SF score will be calculated electronically, from subject 
eDiary entries.  Sites will receive a notification from the IXRS that the subject meets 
the SF score requirement (SF ≥ 1) for performing the endoscopy at Screening Visit 2. 
8.2.2 Screening: Week -4 to -1:  Endoscopy Visit (Visit 2) 
•
Verify subject meets all the inclusion criteria and none of the exclusion criteria
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Confirm subject has had no liquids six (6) hours prior to lower endoscopy
(flexible sigmoidoscopy or colonoscopy)
•
Confirm subject performed bowel preparation at PI discretion (e.g., two [2] Fleet
enemas 1.5 hours before procedure)
•
Perform lower endoscopy (flexible sigmoidoscopy or colonoscopy)

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•
Obtain biopsy for histopathology (3 samples)
•
Obtain biopsy for mucosal genomic analyses (1 sample)
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
Note: The Three-Component Modified Mayo Score will be calculated electronically, 
from subject eDiary entries and central endoscopy read, to determine subject 
eligibility.  Sites will receive an eligibility notification from the IXRS confirming if 
the subject is eligible to be randomized into the protocol (Three-Component 
Modified Mayo Score 3 to 7, inclusive), or is ineligible (screen failure).  
8.2.3 Pre-Treatment: Week 0 (Visit 3) 
8.2.3.1 Pre-dosing 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Confirm eligibility review has been completed by Medical Monitor, pre-
randomization, for final eligibility decision by PI
•
Perform focused physical exam
•
Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory
rate, temperature)
•
Obtain weight
•
Obtain urine sample pre-dose for pregnancy testing; should be performed and
reported as negative prior to dosing. (WOCBP only)
•
Blood sampling pre-dose for hematology, blood chemistry
•
Blood for CRP
•
Perform IBDQ
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
8.2.3.2 Dosing 
•
Perform randomization in IXRS
•
Dispense pre-treatment drug supply
•
Begin pre-treatment drug dosing (observe subject one [1] hour post-dosing)
•
Review stool sample collection, handling and storage instructions with subject
•
Provide stool sample collection kit to subject
•
Begin adverse event monitoring

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8.2.4 Induction Treatment: Week 1 +/-1d (Visit 4) 
8.2.4.1 Pre-dosing: 
•
Concomitant medications
•
Concomitant procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Return any remaining pre-treatment drug and all bottles dispensed
•
Review drug compliance
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
Blood sampling pre-dose for hematology, blood chemistry
•
Blood and Serum for future medical research
•
Subject to return stool sample collected at home and ship to the central
laboratory
•
Review stool sample collection, handling and storage instructions with
subject
8.2.4.2 Dosing: 
•
Begin treatment period drug dosing (observe subject one [1] hour post-dosing)
•
Dispense study drug for daily dosing
•
Continue adverse event monitoring
•
Provide stool collection kit to subject for next clinic visit
8.2.5 Induction Treatment: Week 3 +3d (Visit 5) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Provide stool sample collection kit to subject
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Dispense study drug for daily dosing
•
Continue adverse event monitoring
•
Return all unused study drug and any bottles dispensed
•
Review drug compliance
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
8.2.6 Induction Treatment: Week 7 +3d (Visit 6) 
•
Concomitant Medications
•
Concomitant Procedures for UC

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•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Return all unused study drug and any bottles dispensed
•
Review drug compliance
•
Dispense study drug for daily dosing
•
Continue adverse event monitoring
•
Provide stool collection kit to subject for next clinic visit
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review Subject eDiary for compliance
8.2.7 Induction Treatment: Week 11 +3d (End of Induction Treatment) (Visit 7) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Perform focused physical exam
•
Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory
rate, temperature)
•
Obtain weight
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
IBDQ
•
Confirm subject has had no liquids six (6) hours prior to lower endoscopy
(flexible sigmoidoscopy or colonoscopy)
•
Confirm subject has performed bowel preparation at PI discretion (e.g. two [2]
Fleet enemas 1.5 hours before procedure)
•
Perform lower endoscopy (flexible sigmoidoscopy or colonoscopy)
•
Obtain biopsy for histopathology (3 samples)
•
Obtain biopsy for mucosal genomic analyses (1 sample)
•
Note: Three-Component Modified Mayo Score will be calculated electronically,
from subject eDiary entries and central endoscopy read
•
Return all unused study drug and any bottles dispensed
•
Review drug compliance
•
Collect blood and ship to the central laboratory for evaluation of:
o
Hematology
o
Blood Chemistry
o
CRP
o
Blood and Serum for Future Biomedical research
•
Subject to return stool sample collected at home (pre-liquid diet for endoscopy)
and ship to the central laboratory
•
Fecal calprotectin

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•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
Provide stool collection kit to subject for next clinic visit
•
Continue adverse event monitoring
8.2.8 Induction Treatment: Unscheduled Visit 
See Section 8.2.25, Unscheduled Visits. 
Determining Subjects’ Remitter vs. Non-Remitter Status 
The lower endoscopy performed at the Week 11 visit will be scored, and the Three-
Component Modified Mayo Score will be calculated electronically from subject eDiary 
entries and endoscopic subscore to determine if the subject achieved clinical remission 
(See Section 3, Definitions) at the end of the 10-week Induction Treatment period.   
Subjects who achieve clinical remission at the end of the 10-week Induction Treatment 
period will be re-randomized into the Maintenance Treatment period, to receive either a 
SER-287 Maintenance Dose, once-weekly, or matching placebo, for 26 weeks. 
Subjects who did not achieve clinical remission at the end of the 10-week Induction 
Treatment period will enter the Open-Label Extension arm, where they will receive six 
(6) days of vancomycin pre-treatment followed by 10 weeks of SER-287 (Induction
Dose), once-daily.
Maintenance Treatment Period – Remitters 
8.2.9 Maintenance Treatment: M-Week 12 +/-2d (Visit M-1) 
8.2.9.1 Pre-dosing: 
•
Concomitant medications
•
Concomitant procedures for UC
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
Provide stool collection kit to subject for next clinic visit
8.2.9.2 Dosing: 
•
Perform re-randomization in IXRS
•
Begin treatment period drug dosing.  Subject to take Week 12 dose on site
(observe subject one [1] hour post-dosing)
•
Dispense study drug for weekly dosing

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Continue adverse event monitoring
8.2.10 Maintenance Treatment: M-Week 16 +3d (Visit M-2) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Return all unused study drug and any bottles dispensed
•
Review Study Drug Compliance
•
Dispense study drug for weekly dosing
•
Provide stool collection kit to subject for next clinic visit
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Continue adverse event monitoring
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
8.2.11 Maintenance Treatment: M-Week 20 +3d (Visit M-3) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Return all unused study drug and any bottles dispensed
•
Review drug compliance
•
Dispense study drug for weekly dosing
•
Provide stool collection kit to subject for next clinic visit
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
Continue adverse event monitoring
8.2.12 Maintenance Treatment: M-Week 24 +3d (Visit M-4) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Perform focused physical exam
•
Return all unused study drug and any bottles dispensed
•
Review drug compliance
•
Dispense study drug for weekly dosing
•
Provide stool collection kit to subject for next clinic visit
•
Subject to return stool sample collected at home and ship to the central laboratory

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Continue adverse event monitoring
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
8.2.13 Maintenance Treatment: M-Week 28 +3d (Visit M-5) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Return all unused study drug and any bottles dispensed
•
Review drug compliance
•
Dispense study drug for weekly dosing
•
Provide stool collection kit to subject for next clinic visit
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Continue adverse event monitoring
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
8.2.14 Maintenance Treatment: M-Week 32 +3d (Visit M-6) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Return all unused study drug and any bottles dispensed
•
Review drug compliance
•
Dispense study drug for weekly dosing
•
Provide stool collection kit to subject for next clinic visit
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Continue adverse event monitoring
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
8.2.15 Maintenance Treatment: M-Week 37 +3d (Visit M-7) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Perform focused physical exam
•
Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory
rate, temperature)
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
IBDQ

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•
Confirm subject has had no liquids six (6) hours prior to lower endoscopy
(flexible sigmoidoscopy or colonoscopy)
•
Confirm subject has performed bowel preparation at PI discretion (e.g. two [2]
Fleet enemas 1.5 hours before procedure)
•
Perform lower endoscopy (flexible sigmoidoscopy or colonoscopy)
•
Obtain biopsy for histopathology (3 samples)
•
Obtain biopsy for mucosal genomic analyses (1 sample)
•
Note: Three-Component Modified Mayo Score will be calculated electronically,
from subject eDiary entries and central endoscopy read
•
Obtain weight
•
Return all unused study drug and any bottles dispensed
•
Review drug compliance
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Fecal calprotectin
•
Collect blood and ship to the central laboratory for evaluation of:
o
Hematology
o
Blood chemistry
o
CRP
o
Blood and Serum for Future Biomedical Research
•
Continue adverse event monitoring
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
End of eDiary completion; subject to leave eDiary device on-site
NOTE: If a subject in the Maintenance Treatment Arm experiences a UC flare during 
the first 13 weeks of Maintenance Treatment (prior to M-Week 24), the subject will have 
the option to enter the Open-Label Extension Arm of the study and receive pre-treatment 
with vancomycin followed by 10 weeks of open-label treatment with SER-287.  
8.2.16 Maintenance Treatment – Long-Term Safety Follow-Up: Phone Calls Every 
Four (4) Weeks +/-3d (Visits M-8 – M-13) 
•
During the first four (4) weeks of the Long-Term Safety Follow-Up Period,
AEs/SAEs/AESIs, concomitant procedures, and concomitant medications will be
collected.
•
Continue adverse event monitoring; only SAEs/AESIs and concomitant
medications associated with SAEs/AESIs will be collected for the remainder of
the long-term safety follow-up period.   Concomitant UC medications and UC
procedures, and any changes to these, will be collected throughout the entirety of
the Long-Term Safety Follow-Up Period.

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8.2.17 Maintenance Treatment: Unscheduled Visit 
See Section 8.2.25, Unscheduled Visits. 
Open-Label Extension Arm – Non-Remitters 
8.2.18 Open-Label Extension: OL-Week 0 +/-2d (Visit OL-1) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Register subject in IXRS for Open-Label Extension arm
•
Dispense pre-treatment medication to subject
•
Administer first dose of vancomycin pre-treatment in clinic
•
Dispense two (2) weeks of Open-Label study drug for daily dosing and provide
instructions to subject to start study drug after completing pre-treatment
medication
•
Provide stool collection kit to subject for next clinic visit
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
Continue adverse event monitoring
8.2.19 Open-Label Extension: OL-Week 1 +/-1d (Visit OL-2) 
•
Provide stool collection kit to subject for next clinic visit
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Subject to return stool sample collected at home and ship to the central
laboratory.  The stool sample may be returned to clinical site via courier or by the
subject.
8.2.20 Open-Label Extension: OL-Week 3 +3d (Visit OL-3) 
•
Concomitant medications
•
Concomitant procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Return any remaining pre-treatment and study drug and all bottles dispensed
•
Review drug compliance
•
Dispense study drug for daily dosing
•
Subject to return stool sample collected at home and ship to the central
laboratory
•
Provide stool collection kit to subject for next clinic visits
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
Continue adverse event monitoring

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8.2.21 Open-Label Extension: OL-Week 7 +3d (Visit OL-4) 
•
Concomitant medications
•
Concomitant procedures for UC
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Return any remaining Open-Label study drug and all bottles dispensed
•
Review study drug compliance
•
Provide stool collection kit to subject for next clinic visits
•
Dispense study drug for daily dosing
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
Continue adverse event monitoring
8.2.22  Open-Label Extension: OL-Week 11 +3d (Visit OL-5) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Perform focused physical exam
•
IBDQ
•
Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory
rate, temperature)
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Obtain weight
•
Confirm subject has had no liquids six (6) hours prior to lower endoscopy
(flexible sigmoidoscopy or colonoscopy)
•
Confirm subject has performed bowel preparation at PI discretion (e.g. two [2]
Fleet enemas 1.5 hours before procedure)
•
Perform lower endoscopy (flexible sigmoidoscopy or colonoscopy)
•
Obtain biopsy for histopathology (3 samples)
•
Obtain biopsy for mucosal genomic analyses (1 sample)
•
Note: Three-Component Modified Mayo Score will be calculated electronically,
from subject eDiary entries and central endoscopy read
•
Return all unused study drug and any bottles dispensed
•
Review study drug compliance
•
Collect blood and ship to the central laboratory for evaluation of:
o
Hematology
o
Blood chemistry
o
CRP
•
Blood and serum for future biomedical research

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•
Continue adverse event monitoring
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
•
End of eDiary completion; subject to leave eDiary device on-site
8.2.23 Open-Label Extension – Long-Term Safety Follow-Up: Phone Calls Every 
Four (4) Weeks for 26 Weeks/EoS +/-3d (Visits OL-6 – OL-11) 
•
During the first four (4) weeks of the Long-Term Safety Follow-Up Period,
AEs/SAEs/AESIs, concomitant procedures, and concomitant medications will be
collected
•
Continue adverse event monitoring; only SAEs/AESIs and concomitant
medications associated with the treatment of SAEs/AESIs will be collected for
the remainder of the long-term safety follow-up period.  Concomitant UC
medications and UC procedures, and any changes to these, will be collected
throughout the entirety of the Long-Term Safety Follow-Up Period.
8.2.24 Open-Label Extension: Unscheduled Visit 
See Section 8.2.25, Unscheduled Visits. 
8.2.25 Unscheduled Visits 
To accommodate scheduling of clinic visits and/or endoscopies, assessments & 
procedures for an Unscheduled Visit do not need to take place during one (1) clinic visit. 
The Unscheduled Visit may be used for dispensation of study drug, as needed.   
For subjects who experience disease worsening (as defined in Section 3.6, Disease 
Worsening), an Unscheduled Visit may be used by the PI to determine if the subject is 
experiencing a UC flare. 
The Unscheduled Visit can serve as an 'End of Treatment' visit for a subject who ends 
treatment early in the study but will continue to be followed for safety, or for subjects 
who decide to leave the study early and not be followed for safety.  If subjects decide to 
end treatment early or early terminate from the study, all study IP should be returned by 
the subject. 
8.2.25.1 Unscheduled Visit for Reasons Other than UC Flare Assessment or EoT (Pre-
Treatment, Induction, Maintenance and Open-Label) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Continue Adverse Event Monitoring
•
Focused Physical Exam
•
IBDQ
•
Assess Vital Signs (systolic and diastolic pressure, heart rate, respiratory rate,
temperature)
•
Collect blood and ship to the central laboratory for evaluation of:

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o
Hematology
o
Blood Chemistry
o
Blood and Serum for Future Biomedical research
•
Subject to return stool sample collected at home and ship to the central laboratory
•
Fecal calprotectin
8.2.25.2 Unscheduled Visit for UC Flare Assessment (Pre-Treatment, Induction, 
Maintenance and Open-Label) 
•
Concomitant Medications
•
Concomitant Procedures for UC
•
Continue Adverse Event Monitoring
•
Focused Physical Exam
•
IBDQ
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Assess Vital Signs (systolic and diastolic pressure, heart rate, respiratory rate,
temperature)
•
Obtain weight
•
Confirm subject has had no liquids six (6) hours prior to lower endoscopy
(flexible sigmoidoscopy or colonoscopy)
•
Confirm subject has performed bowel preparation at PI discretion (e.g. two [2]
Fleet enemas 1.5 hours before procedure)
•
Perform lower endoscopy (flexible sigmoidoscopy or colonoscopy)
•
Obtain biopsy for histopathology (3 samples)
•
Obtain biopsy for mucosal genomic analyses (1 sample)
•
Note: Three-Component Modified Mayo Score will be calculated electronically,
from subject eDiary entries and central endoscopy read
•
Collect blood and ship to the central laboratory for evaluation of:
o
Hematology
o
Blood Chemistry
o
CRP
o
Blood and Serum for Future Biomedical research
•
Subject to return stool sample collected at home (pre-liquid diet for endoscopy)
and ship to the central laboratory
•
Fecal calprotectin
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
8.2.26 End of Treatment Visit 
Perform the following assessments and procedures: 
•
Concomitant Medications
•
Concomitant Procedures for UC

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•
Perform focused physical exam
•
Assess vital signs (systolic and diastolic blood pressure, heart rate, respiratory
rate, temperature)
•
Obtain weight
•
IBDQ
•
Obtain urine sample for pregnancy testing (WOCBP only)
•
Confirm subject has had no liquids six (6) hours prior to lower endoscopy
(flexible sigmoidoscopy or colonoscopy)
•
Confirm subject has performed bowel preparation at PI discretion (e.g. two [2]
Fleet enemas 1.5 hours before procedure)
•
Perform lower endoscopy (flexible sigmoidoscopy or colonoscopy)
•
Obtain biopsy for histopathology (3 samples)
•
Obtain biopsy for mucosal genomic analyses (1 sample)
•
Note: Three-Component Modified Mayo Score will be calculated electronically,
from subject eDiary entries and central endoscopy read
•
Return all unused study drug and any bottles dispensed
•
Review study drug compliance
•
Collect blood and ship to the central laboratory for evaluation of:
o
Hematology
o
Blood Chemistry
o
CRP
o
Blood and Serum for Future Biomedical research
•
Subject to return stool sample collected at home (pre-liquid diet for endoscopy)
and ship to the central laboratory
•
Subject eDiary (daily rectal bleeding, stool frequency)
•
Review subject eDiary for compliance
8.2.27 Handling of Withdrawals and Discontinuations of Treatment 
The primary reason for withdrawal from study treatment and/or withdrawal from the 
study will be recorded in an electronic case report form (eCRF).  
Subjects who voluntarily withdraw, or who are withdrawn from the study during 
treatment (Pre-Treatment/Induction/Maintenance/Open-Label) will be encouraged to 
complete the End of Treatment Visit.  The End of Treatment Visit procedures are listed 
in Section 8.2.26, End of Treatment Visit. Although subjects are free to withdraw at any 
time, subjects will be encouraged to remain in the study for long term follow-up safety 
evaluation. 

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o
Clinical remission co-endpoints: symptomatic remission and endoscopic
remission after 10 weeks of induction treatment
9.1.4 Exploratory Efficacy Endpoints 
•
Clinical remission at the end of maintenance treatment and at the end of open-
label treatment
•
Endoscopic improvement at the end of open-label treatment
•
Endoscopic remission at the end of maintenance treatment and at the end of open-
label treatment
•
Histological mucosal healing at the end of maintenance treatment and at the end
of open-label treatment
•
Symptomatic remission (rectal bleeding and stool frequency) over time
•
Clinical remission after 10 weeks of induction treatment for each SER-287 donor
used in the induction treatment period
•
IBDQ scores after 10 weeks of induction treatment, at the end of maintenance
treatment and at the end of open-label treatment
•
Serum biomarkers: CRP after 10 weeks of induction treatment (Week 11), at the
end of maintenance treatment and at the end of open-label treatment
•
Fecal biomarkers: fecal calprotectin levels after 10 weeks of induction treatment
(Week 11), at the end of maintenance treatment and at the end of open-label
treatment
•
Composition of the intestinal microbiome through the end of the maintenance
treatment and open-label treatment periods
•
Signatures of host and microbial functional responses through the end of the
maintenance treatment and open-label treatment periods
9.1.5 Safety Endpoints 
•
Incidence of AEs, SAEs and AESIs for each treatment and each SER-287 donor
•
Laboratory evaluation results
•
Vital sign measurements
•
Physical examination findings
9.2 
Study Subjects 
9.2.1 Disposition of Subjects 
The number and percentage of subjects entering and completing the clinical study will be 
presented, by treatment group. 
9.2.2 Protocol Deviations 
Protocol deviations will be listed by subject. 
9.2.3 Analysis Populations 
Intent-to-Treat Analysis Population: The Intent-to-Treat (ITT) Population will consist of 
all subjects who are randomly assigned, including 
those who are not exposed to any study drug, and 

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will be analyzed based on the treatment to which 
they were randomized.  The ITT population will be 
the primary analysis population for all efficacy 
endpoints. 
Modified Intent-to-Treat 1 Population: The Modified Intent-to-Treat 1 (mITT-1) 
Population will consist of all randomized subjects 
with a baseline evaluation, who have active mild-
to-moderate UC and receive any amount of study 
drug, and will be analyzed based on the treatment 
to which they were randomized.   
Modified Intent-to-Treat 2 Population: The Modified Intent-to-Treat 2 (mITT-2) 
Population will consist of all randomized subjects 
with a baseline evaluation, who have active mild-
to-moderate UC and receive any amount of study 
drug, and will be analyzed based on the treatment 
to which they are randomized.  Subjects who are 
confirmed to have normal histology at baseline will 
be excluded from this analysis population. 
Per Protocol Population:  
The Per Protocol (PP) Population will consist of 
subjects from the mITT-2 Population who do not 
have any major protocol deviations.  The details of 
the PP Population will be provided in the SAP and 
defined before unblinding of the data. 
Microbiome Modified Intent-to-Treat: The Microbiome Modified Intent-to-Treat 
(mcITT) Population will be used for analysis of 
microbiome data.  It will consist of all randomized 
subjects with an evaluable stool sample collected at 
baseline, and at least one (1) evaluable stool sample 
collected after the start of dosing, who are exposed 
to any amount of study drug, and will be analyzed 
based on the treatment to which they are 
randomized. 
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 are randomly assigned.  All safety analyses 
will be conducted based on the Safety Population. 
All clinical efficacy analyses will be conducted in the ITT population, and in the mITT-1, 
mITT-2, PP and Safety populations as sensitivity analyses, as appropriate. 
All microbiome alterations analyses will be conducted in the mcITT population. 

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9.3 
Multiplicity Adjustment 
Adjustments for multiple testing will be made to test the primary efficacy and key 
secondary efficacy endpoints.  A fixed-sequence method will be used to maintain a 
study-wide 2-sided Type I error rate of 0.05.  Testing of the key hypotheses will be 
conducted in the following order, all at the same significance level (2-sided α = 0.05): 
1.
H01: No difference in clinical remission rates after 10 weeks of induction
treatment between Arm B (SER-287 at Induction Dose after pre-treatment with
vancomycin) vs. Arm A (pre-treatment with placebo followed by treatment with
placebo) in the ITT population
2.
H02: No difference in clinical remission rates after 10 weeks of induction
treatment between Arm C (SER-287 at Step-Down Induction Dose after pre-
treatment with vancomycin) vs. Arm A (pre-treatment with placebo followed by
treatment with placebo) in the ITT population
3.
H03: No difference in endoscopic improvement rates after 10 weeks of induction
treatment between Arm B (SER-287 at Induction Dose after pre-treatment with
vancomycin) vs. Arm A (pre-treatment with placebo followed by treatment with
placebo) in the ITT population
4.
H04: No difference in endoscopic improvement rates after 10 weeks of induction
treatment between Arm C (SER-287 at Step-Down Induction Dose after pre-
treatment with vancomycin) vs. Arm A (pre-treatment with placebo followed by
treatment with placebo) in the ITT population
Testing of later hypotheses in the sequence stops as soon as failure to show statistical 
significance at the 2-sided 0.05 level is observed in a hypothesis earlier in the sequence. 
9.4 
General Considerations 
All clinical efficacy, safety and tolerability, intestinal microbiome, and biomarker data 
will be listed and presented in descriptive summaries by treatment arm, visit and time 
point. At a minimum, continuous data will be summarized by study arm using descriptive 
statistics (number of subjects, mean, standard deviation, minimum, median and 
maximum).  Categorical data will be summarized by study arm using frequency tables 
(number of subjects and percentage). 
Selected clinical efficacy and biomarker data will be presented in treatment mean (+/-
standard deviation [SD]) profile plots.   
All statistical analyses will be performed using SAS® Version 9.3 or later. 
9.5 
Efficacy Analyses 
9.5.1 Timing of Analyses 
9.5.1.1 At the end of the Induction Treatment period 
Seres will conduct an unblinded analysis of the efficacy and safety endpoints when all 
planned subjects in the study are enrolled, have been evaluated for the primary/key 

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secondary efficacy endpoints and have completed their Induction Treatment (Week 11 
[Visit 7]) or have terminated from the study prematurely prior to the Week 11 [Visit 7]. 
Key unblinded efficacy and safety summary tables will be generated at this time.  
Limited personnel at Seres will have access to the unblinded tables, listings and figures 
(TLFs).   A detailed unblinding plan will be drafted and finalized at the same time that 
the SAP is finalized.  
All clinical data generated during the primary study period (Screening Visit 1 through 
Week 11 [Visit 7]) for all subjects enrolled in the study will be entered in the database, 
cleaned and locked prior to the unblinding.  No changes to any locked data in the 
database will be permitted, unless deemed to be highly warranted. Therefore, all efficacy 
results evaluated up until this primary study period will be considered final.  A 
comparison of the data at the time of this unblinding and at the end of the study will be 
performed.  An audit trail of any changes made to the locked data will be available.  
9.5.1.2 At the end of the Maintenance Treatment period 
Seres will conduct an unblinded analysis of the safety and exploratory efficacy endpoints 
when all subjects who were re-randomized in the maintenance arm have been evaluated 
for the exploratory efficacy endpoints, and have completed their maintenance treatment, 
or have terminated the study prematurely prior to Week 37 (Visit M-7). 
Key unblinded efficacy and safety summary tables will be generated at this time.  
Limited personnel at Seres will have access to the unblinded tables, listings and figures 
(TLFs).    
All clinical data generated during the maintenance period (Week 11 through Week 37 
[Visit M-7]) for all subjects enrolled in the maintenance arm will be entered in the 
database, cleaned and locked prior to the unblinding.  No changes to any locked data in 
the database will be permitted, unless deemed to be highly warranted.  Therefore, all 
efficacy results evaluated up until this time for the maintenance arm will be considered 
final at the time of the analysis.  A comparison of the data at the time of this unblinding 
and at the end of the study will be performed.  An audit trail of any changes made to the 
locked data will be available. 
9.5.1.3 At the end of the Long-Term Safety Follow-Up period 
At the end of the Long-Term Safety Follow-Up period, after final database lock, all AE 
summary tables will be re-generated to include any additional safety findings from this 
period.  All other TLFs will also be re-run to ensure that any changes to the database that 
may have occurred since the earlier analyses are reflected in the final TLFs.  All changes 
in the efficacy results from the previous analyses will be described in the Clinical Study 
Report (CSR). 
9.5.2 Statistical Analysis and Significance Level 
Statistical significance tests, if reported, will be two-sided and will be presented as 
relative measures of the strength of association to the active SER-287 treatment arm 
(Arms B and C) for comparison with the placebo arm (Arm A) among study endpoints.  

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Details of the statistical analysis will be addressed in the SAP, finalized prior to the time 
the primary study period data is declared complete and final and any study unblinding. 
9.5.3 Missing or Spurious Data 
Every effort will be made to collect all data at specified timepoints, according to the 
schedule of study events. 
For analysis of the binary efficacy endpoints (i.e. clinical remission, endoscopic remission 
and clinical remission with normalization of stool frequency during the induction period), 
subjects with missing values will be assigned an outcome of failure for the endpoint, if  
(i)
the subject discontinued study treatment prior to Study Day 48, OR
(ii)
did not have a post-baseline endoscopy done during the induction period, OR
(iii)
if data is missing for any of the subscores needed for the Week 11 assessments
at the end of the induction period, such that the endpoint cannot be calculated.
The description of the handling of missing data for individual components of the Three-
Component Modified Mayo Score, specifically stool frequency and rectal bleeding, are 
described in Appendix 2. 
As sensitivity analyses, the primary endpoint and the key secondary endpoint will also be 
analyzed based on the last observation carried forward (LOCF) approach. Subjects who 
only have baseline values will be treated as failures for the endpoint in the LOCF 
analysis. The observed-case analyses will also be conducted where missing values will 
be excluded in the analyses. 
For continuous secondary endpoints, such as histological mucosal healing, missing 
values will not be imputed. The analyses will be based on the observed-case data where 
missing values will be excluded in the analyses. 
Handling of missing data for other endpoints will be specified in the SAP. 
9.5.4 Analysis of the Primary Efficacy Endpoint 
The primary efficacy outcome measure for this study will be the difference in clinical 
remission rates after 10 weeks of induction treatment between SER-287 (Induction Dose 
after pre-treatment with vancomycin – Arm B) and placebo (Arm A).  The primary 
efficacy endpoint analysis will be based on the CMH test, stratified by endoscopic score 
at baseline (1-2 vs. 3), and UC medications at baseline (5-ASA alone vs. 
immunomodulators with or without 5-ASA vs. none) in the ITT population. 
9.5.5 Analysis of the Key Secondary Efficacy Endpoints 
The key secondary efficacy endpoints will be analyzed using the same method used for 
the primary efficacy endpoint. 
Sensitivity Analyses for the primary and key secondary efficacy endpoint will be 
performed in the mITT-1, mITT-2, Safety and PP populations. 

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9.5.6 Analyses of Other Secondary Efficacy Endpoints 
All other dichotomous secondary efficacy endpoints will be analyzed using the same 
method used for the primary efficacy endpoint. 
For histological mucosal healing, analysis will be based on the change from baseline 
score using RHI (Mosli et al., 2017) and analyzed by an analysis of covariance 
(ANCOVA) test, with treatment, endoscopic score at baseline and UC medications at 
baseline as factors in the model.  The primary analysis population for this endpoint will 
be the mITT-2 population. 
All clinical efficacy analyses will be conducted in the ITT population, unless otherwise 
stated, and in the mITT-1, mITT-2 and PP populations as sensitivity analyses, as 
appropriate. 
9.5.7 Analyses of Exploratory Endpoints 
Details of the methods used for the analyses of the exploratory endpoints will be 
provided in the SAP. 
9.6 
Safety Analyses 
9.6.1 Adverse Events 
A TEAE is any adverse event (AE) that newly appeared, increased in frequency, or 
worsened in severity after initiation of study drug (including the pre-treatment period). 
Safety summaries of TEAEs will be presented by treatment group at the end of the pre-
treatment period (Week 1), Week 3, Week 7, after 10 weeks of induction treatment 
(Week 11), at the end of Maintenance Treatment or Open-Label Treatment and at end-of-
study, with selected safety summaries also presented by baseline endoscopic subscore 
and baseline UC medication stratum.  The number and percentage of subjects with 
TEAEs will be tabulated by system organ class and preferred term (PT) for each 
treatment group and stratum.  Serious TEAEs, AESIs and TEAEs leading to study 
discontinuation will be similarly tabulated.  Summaries of TEAEs by maximum severity 
and by maximum relationship to study drug will also be summarized by system organ 
class and PT.  
Selected safety summaries will also be provided by SER-287 donor. 
A listing of all TEAEs will be provided. 
All safety analyses will be conducted in the Safety Population, unless specified 
otherwise.  Subjects will be analyzed according to the treatment they actually received, 
rather than that to which they are randomly assigned.  Adverse events will be coded by 
using the Medical Dictionary for Regulatory Activities (MedDRA).   

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9.6.2 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. 
9.6.3 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. 
9.6.4 Physical Examination Findings 
Abnormal clinically significant physical examination (PE) finding will be reported as 
medical history (MH) or as an AE.  
9.6.5 Pharmacokinetic Analyses 
Not applicable 
9.7 
Gastrointestinal Tract Microbiome 
The gastrointestinal microbiome of subjects will be characterized using genomic data 
sets generated from stool collected at the time points defined above in the Schedule of 
Events.  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 phylogenetic clade and/or species and further, to 
define the relative proportion of each species or taxon relative to all other species or taxa 
in a given sample.  Engraftment of SER-287 taxa will be measured and analyzed as 
defined in Section 9.7.1, Microbiome Secondary Endpoint Data Analysis. 
9.7.1 Microbiome Secondary Endpoint Data Analysis 
Engraftment of spore-forming bacteria in SER-287 will be assessed by examining the 
richness of spore-forming taxa found in drug product lots which appear newly in subject 
stool at one (1) or more timepoints after the initiation of treatment with SER-287 
(∆Sobs_spore_dose).  The nonparametric one-sided Mann-Whitney U test will be used to 
determine if there is a greater change in ∆Sobs_spore_dose in subjects receiving 
SER-287 relative to subjects receiving placebo. 
Further details will be included in the microbiome SAP. 

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9.8 
Interim Analyses 
Two unblinded analyses will be conducted prior to the completion of the entire study, 
specifically at the end of the induction period and at the end of the maintenance period.  
Please refer to Section 9.5.1, Timing of Analyses, for further details on these analyses.  
9.9 
Determination of Sample Size 
The planned sample size for this study is 67 subjects per treatment arm for a total sample 
size of 201 subjects. Assuming a clinical remission rate of 29% in the SER-287 arms and 
a clinical remission rate of 9% in the placebo arm, this sample size will provide 86% 
power to detect a difference of 20% in clinical remission rates between SER-287 to 
placebo, using a 2-sided significance level of 0.05. 
A placebo rate of 7% was derived from the weighted average of the placebo rates 
observed in the tofacitinib Phase 2 (Sandborn et al., 2012), 3A and 3B (Sandborn et al., 
2017) studies, and the ozanimod induction studies (Sandborn et al., 2016).  These 
four (4) studies were chosen as the basis for the placebo rate because each utilized a 
central reader to determine subjects’ endoscopic subscores.  However, due to the 
inclusion of mild subjects and those with an endoscopic subscore of 1 in the SERES-201 
study, who may have a higher placebo response rate, the assumed placebo rate was 
increased to 9%.  The clinical remission rate that was used for the SER-287 arm was 
based on the re-analysis of the clinical remission rate in the vancomycin/SER-287 daily 
arm in the SERES-101 Phase 1B study, and applying the definition of clinical remission 
for the SERES-201 study; additionally, only subjects with a baseline Three-Component 
Modified Mayo Score between 3 and 7, inclusive, and a baseline stool frequency 
subscore ≥1 were included, (38.5% with 95% CI: 15.1%, 67.7%).  The clinical remission 
rate was decreased to 29% to account for the small sample size in this SERES-101 arm 
(n=13).   

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10 ADMINISTRATIVE REQUIREMENTS 
10.1 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.
10.2 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, informed consent form 
(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. 
10.3 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. 

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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. 
10.4 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. 
10.5 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. 
10.6 Future Use of Stored Specimens 
The sponsor may, where permitted by local regulations, conduct future biomedical 
research on specimens (including blood, serum, stool and biopsies) 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. 
10.7 Study Monitoring 
Regular monitoring is defined in ICH Guidance for Industry E6 R2 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, GCP, and the applicable regulatory 
requirement(s).”  The purpose of monitoring is to verify that: 

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•
Rights and wellbeing of the human subjects are protected.
•
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. 
10.8 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 must be 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.  
In addition to capturing the user identification as part of the audit trail for all data entry, 
the eCRF will allow for application of electronic signatures.  The Investigator or 
designated Sub-Investigator, 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. 

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10.9 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 End-of-Study
•
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)

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Laughlin, R.C., Gomez, G., Wu, J., Lawhon, S.D., et al. (2013). Host-derived nitrate 
boosts growth of E. coli in the inflamed gut. Science 339, 708–711. 
Wu, G.D., Bushmanc, F.D., and Lewis, J.D. (2013). Diet, the human gut microbiota, and 
IBD. Anaerobe 24, 117–120. 
Xavier, R.J., and Podolsky, D.K. (2007). Unravelling the pathogenesis of inflammatory 
bowel disease. Nature 448, 427–434. 

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12 APPENDICES 
12.1 Appendix 1: Mayo Score (Schroeder et al., 1987) 
Stool frequency*  
0= Normal no. of stools for this patient 
1= 1-2 stools more than normal  
2= 3-4 stools more than normal  
3= 5 or more stools more than normal 
Rectal bleeding**
0= No blood seen 
1= Streaks of blood with stool less than half the time 
2= Obvious blood with stool most of the time 
3= Blood alone passed 
Findings of flexible proctosigmoidoscopy  
0= Normal or inactive disease 
1= Mild disease (erythema, decreased vascular pattern, mild friability)  
2= Moderate disease (marked erythema, absent vascular pattern, friability, erosions) 
3= Severe disease (spontaneous bleeding, ulceration)  
Physician’s global assessment*** 
0= Normal 
1= Mild disease 
2= Moderate disease  
3= Severe disease  
* Each patient served as his or her own control to establish the degree of abnormality of the stool
frequency.
** The daily bleeding score represented the most severe bleeding of the day. 
*** The physician’s global assessment acknowledged the three other criteria, the patient’s record of 
abdominal discomfort and general sense of well-being, and other observations, such as physical findings 
and the patient’s performance status. 
Schroeder, K.W., Tremaine, W.J., Ilstrup, D.M., (1987). Coated Oral 5-Aminosalicylic Acid Therapy for 
Mildly to Moderately Active Ulcerative Colitis. N. Engl. J. Med. 317(26), 1625-1629. 

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12.3 Appendix 3: Inflammatory Bowel Disease Questionnaire (Guyatt et al., 1989) 
INSTRUCTIONS FOR SELF-ADMINISTERED IBDQ 
This questionnaire is designed to measure the effects of your inflammatory bowel disease 
on your daily function and quality of life. You will be asked about symptoms you have 
been having as a result of your bowel disease, the way you have been feeling in general, 
and how your mood has been.  
There are two versions of this questionnaire, the IBDQ and IBDQ-Stoma. If you have a 
colostomy or ileostomy, you should complete the IBDQ-Stoma. Questions 1, 5, 17, 22, 
24 and 26 are slightly different in each version. Be sure you have the correct 
questionnaire.  
On this questionnaire there are 32 questions. Each question has a graded response 
numbered from I through 7. Please read each question carefully and answer the number 
which best describes how you have been feeling in the past 2 weeks.  
EXAMPLE 
How often have you felt unwell as a result of your bowel problem in the past 2 weeks? 
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
If you are having trouble understanding a question, STOP for a moment! Think about 
what the question means to you. How is it affected by your bowel problem? Then answer 
the question as best you can. You will have the chance to ask the research assistant 
questions after completing the questionnaire. This takes only a few minutes to complete.  
Copyright © 1989 McMaster University, Hamilton, Ontario, Canada 
The Inflammatory Bowel Disease Questionnaire (IBDQ), authored by Dr. Jan Irvine et al, is the copyright of McMaster University 
(Copyright ©1989, McMaster University). The IBDQ has been provided under license from McMaster University and must not be 
copied, distributed or used in any way without the prior written consent of McMaster University.   
Contact the McMaster Industry Liaison Office at McMaster University, email: milo@mcmaster.ca for licensing details. 

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QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE 
QUESTIONNAIRE (IBDQ) 
This questionnaire is designed to find out how you have been feeling during the last 
2 weeks. You will be asked about symptoms you have been having as a result of your 
inflammatory bowel disease, the way you have been feeling in general, and how your 
mood has been.  
1. How frequent have your bowel movements been during the last two weeks? Please
indicate how frequent your bowel movements have been during the last two weeks by
picking one of the options from
1 BOWEL MOVEMENTS AS OR MORE FREQUENT THAN THEY HAVE EVER 
BEEN  
2 EXTREMELY FREQUENT  
3 VERY FREQUENT  
4 MODERATE INCREASE IN FREQUENCY OF BOWEL MOVEMENTS  
5 SOME INCREASE IN FREQUENCY OF BOWEL MOVEMENTS  
6 SLIGHT INCREASE IN FREQUENCY OF BOWEL MOVEMENTS  
7 NORMAL, NO INCREASE IN FREQUENCY OF BOWEL MOVEMENTS 
2. How often has the feeling of fatigue or of being tired and worn out been a problem for
you during the last 2 weeks?  Please indicate how often the feeling of fatigue or tiredness
has been a problem for you during the last 2 weeks by picking one of the options from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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3. How often during the last 2 weeks have you felt frustrated, impatient, or restless?
Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
4. How often during the last 2 weeks have you been unable to attend school or do your
work because of your bowel problem?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
5. How much of the time during the last 2 weeks have your bowel movements been
loose?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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6. How much energy have you had during the last 2 weeks?  Please choose an option
from
1 NO ENERGY AT ALL  
2 VERY LITTLE ENERGY  
3 A LITTLE ENERGY  
4 SOME ENERGY  
5 A MODERATE AMOUNT OF ENERGY 
6 A LOT OF ENERGY  
7 FULL OF ENERGY  
7. How often during the last 2 weeks did you feel worried about the possibility of
needing to have surgery because of your bowel problem.  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
8. How often during the last 2 weeks have you had to delay or cancel a social
engagement because of your bowel problem?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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9. How often during the last 2 weeks have you been troubled by cramps in your
abdomen? Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
10. How often during the last 2 weeks have you felt generally unwell?  Please choose an
option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
11. How often during the last 2 weeks have you been troubled because of fear of not
finding a washroom?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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12. How much difficulty have you had, as a result of your bowel problems, doing leisure
or sports activities you would have liked to have done during the last 2 weeks?  Please
choose an option from
1 A GREAT DEAL OF DIFFICULTY; ACTIVITIES MADE IMPOSSIBLE 
2 A LOT OF DIFFICULTY  
3 A FAIR BIT OF DIFFICULTY  
4 SOME DIFFICULTY  
5 A LITTLE DIFFICULTY  
6 HARDLY ANY DIFFICULTY  
7 NO DIFFICULTY; THE BOWEL PROBLEMS DID NOT LIMIT SPORTS OR 
LEISURE ACTIVITIES  
13. How often during the last 2 weeks have you been troubled by pain in the abdomen?
Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
14. How often during the last 2 weeks have you had problems getting a good night's
sleep, or been troubled by waking up during the night?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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15. How often during the last 2 weeks have you felt depressed or discouraged? Please
choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
16. How often during the last 2 weeks have you had to avoid attending events where
there was no washroom close at hand?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
17. Overall, in the last 2 weeks, how much of a problem have you had with passing large
amounts of gas?  Please choose an option from
1 A MAJOR PROBLEM  
2 A BIG PROBLEM  
3 A SIGNIFICANT PROBLEM 
4 SOME TROUBLE  
5 A LITTLE TROUBLE  
6 HARDLY ANY TROUBLE  
7 NO TROUBLE  

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18. Overall, in the last 2 weeks, how much of a problem have you had maintaining or
getting to, the weight you would like to be at. Please choose an option from
1 A MAJOR PROBLEM  
2 A BIG PROBLEM  
3 A SIGNIFICANT PROBLEM 
4 SOME TROUBLE  
5 A LITTLE TROUBLE  
6 HARDLY ANY TROUBLE  
7 NO TROUBLE  
19. Many patients with bowel problems often have worries and anxieties related to their
illness. These include worries about getting cancer, worries about never feeling any
better, and worries about having a relapse.  In general, how often during the last 2 weeks
have you felt worried or anxious?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
20. How much of the time during the last 2 weeks have you been troubled by a feeling of
abdominal bloating?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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21. How often during the last 2 weeks have you felt relaxed and free of tension?  Please
choose an option from
1 NONE OF THE TIME  
2 A LITTLE OF THE TIME  
3 SOME OF THE TIME  
4 A GOOD BIT OF THE TIME  
5 MOST OF THE TIME  
6 ALMOST ALL OF THE TIME 
7 ALL OF THE TIME  
22. How much of the time during the last 2 weeks have you had a problem with rectal
bleeding with your bowel movements?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
23. How much of the time during the last 2 weeks have you felt embarrassed as a result
of your bowel problem? Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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24. How much of the time during the last 2 weeks have you been troubled by a feeling of
having to go to the bathroom even though your bowels were empty?  Please  choose an
option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
25. How much of the time during the last 2 weeks have you felt tearful or upset?  Please
choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
26. How much of the time during the last 2 weeks have you been troubled by accidental
soiling of your underpants? Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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27. How much of the time during the last 2 weeks have you felt angry as a result of your
bowel problem?  Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
28. To what extent has your bowel problem limited sexual activity during the last 2
weeks?  Please choose an option from
1 NO SEX AS A RESULT OF BOWEL DISEASE  
2 MAJOR LIMITATION AS A RESULT OF BOWEL DISEASE  
3 MODERATE LIMITATION AS A RESULT OF BOWEL DISEASE  
4 SOME LIMITATION AS A RESULT OF BOWEL DISEASE  
5 A LITTLE LIMITATION AS A RESULT OF BOWEL DISEASE  
6 HARDLY ANY LIMITATION AS A RESULT OF BOWEL DISEASE 
7 NO LIMITATION AS A RESULT OF BOWEL DISEASE  
29. How much of the time during the last 2 weeks have you been troubled by nausea or
feeling sick to your stomach?  Please choose an option. from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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30. How much of the time during the last 2 weeks have you felt irritable? Please choose
an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  
31. How often during the past 2 weeks have you felt a lack of understanding from others?
Please choose an option from
1 ALL OF THE TIME  
2 MOST OF THE TIME  
3 A GOOD BIT OF THE TIME  
4 SOME OF THE TIME  
5 A LITTLE OF THE TIME  
6 HARDLY ANY OF THE TIME 
7 NONE OF THE TIME  

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32. How satisfied, happy, or pleased have you been with your personal life during the
past 2 weeks? Please choose one of the following options from
1 VERY DISSATISFIED, UNHAPPY MOST OF THE TIME 
2 GENERALLY DISSATISFIED, UNHAPPY  
3 SOMEWHAT DISSATISFIED, UNHAPPY  
4 GENERALLY SATISFIED, PLEASED  
5 SATISFIED MOST OF THE TIME, HAPPY  
6 VERY SATISFIED MOST OF THE TIME, HAPPY  
7 EXTREMELY SATISFIED, COULD NOT HAVE BEEN MORE HAPPY OR 
PLEASED 
Copyright © 1989 McMaster University, Hamilton, Ontario, Canada 
The Inflammatory Bowel Disease Questionnaire (IBDQ), authored by Dr. Jan Irvine et al, is the copyright of McMaster University 
(Copyright ©1989, McMaster University). The IBDQ has been provided under license from McMaster University and must not be 
copied, distributed or used in any way without the prior written consent of McMaster University.   
Contact the McMaster Industry Liaison Office at McMaster University, email: milo@mcmaster.ca for licensing details. 
Guyatt G, Mitchell A, Irvine EJ, Singer J, Williams N, Goodacre R, Tompkins C. (1989). A New Measure 
of Health Status for Clinical Trials in Inflammatory Bowel Disease. Gastroenterology. 96(3), 804-10.