ECOSPOR III - SER-109 Versus Placebo in the Treatment of Adults With Recurrent Clostridium Difficile Infection

ECOSPOR III is a Phase 3, multicenter, randomized, double-blind, placebo-controlled,
parallel-group study of the safety, tolerability, and efficacy of SER-109 versus placebo in
adult subjects 18 years of age or older with recurrent CDI, defined as: a history of ≥ 3 CDI
episodes within 9 months, inclusive of the current episode. This study is designed to
demonstrate the superiority of SER-109 versus placebo to reduce recurrence of Clostridium
difficile infection (CDI) in adults who have received antibacterial drug treatment for
recurrent CDI (RCDI), based on the proportion of subjects experiencing a CDI recurrence
requiring antibiotic treatment up to 8 weeks after initiation of treatment. Approximately 320
subjects with a history of CDI, diarrhea and a positive C. difficile toxin test result on a
stool sample, who have responded to standard-of-care (SOC) antibiotic treatment will be
enrolled. Subjects will be randomly assigned, in a 1:1 ratio, to 1 of 2 treatment groups
(Treatment Group I [SER-109] or Treatment Group II [Placebo]) and stratified by age (<65
years; ≥65 years), as well as antibiotic regimen for the qualifying episode (vancomycin;
fidaxomicin).

Subjects will receive an oral dose of SER-109 in 4 capsules once daily for 3 consecutive days
in Treatment Group I or matching placebo once daily for 3 consecutive days in Treatment Group
II.

Subjects with confirmed CDI recurrence, as defined in the Protocol, up to 8 weeks after
administration of SER-109 or placebo treatment, and who have completed their Week 8 visit,
may be eligible to enroll in the open- label SER-109 extension study (Study SERES-013).

Inclusion Criteria:

1. Signed informed consent prior to initiation of any study-specific procedure or
treatment. The subject must be able to provide written informed consent and understand
the potential risks and benefits from study enrollment and treatment.

2. Male or female subject ≥ 18 years of age.

3. A qualifying episode of CDI as defined by:

1. ≥ 3 unformed stools per day for 2 consecutive days

2. A positive C. difficile stool toxin assay.

3. The requirement of CDI SOC antibiotic therapy (defined as 10 to 21 days of
treatment with vancomycin [125 mg QID] and/or fidaxomicin [200 mg BID]).

4. An adequate clinical response following SOC antibiotic therapy, defined as (<3
unformed stools in 24 hours) for 2 or more consecutive days before randomization.

Exclusion Criteria:

1. Female subjects who are pregnant, breastfeeding, lactating, or planning to become
pregnant during the study.

2. Known or suspected toxic megacolon and/or known small bowel ileus.

3. Admitted to or expected to be admitted to an intensive care unit for medical reasons
(not just boarding). Note: nursing homes, rehabilitation, assisted living centers and
acute care hospitals are acceptable.

4. Absolute neutrophil count of <500 cells/ml3

5. Major gastrointestinal surgery (e.g. significant bowel resection or diversion) within
3 months before enrollment (this does not include appendectomy or cholecystectomy), or
any history of total colectomy or bariatric surgery (bariatric surgery which does not
disrupt the gastrointestinal lumen, i.e., restrictive procedures such as banding, are
permitted).

6. History of active inflammatory bowel disease (ulcerative colitis, Crohn's disease,
microscopic colitis) with diarrhea believed to be caused by active inflammatory bowel
disease in the past 3 months.

7. Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for
active malignancy (subjects on maintenance chemotherapy may only be enrolled after
consultation with the study medical monitor).

8. Any history of fecal microbiota transplantation (FMT).