Randomized Phase 2 Study of VE303 for Prevention of Recurrent Clostridium Difficile Infection

CONSORTIUM is a randomized, double-blind phase 2 study to evaluate safety, tolerability,
PK/PD, and efficacy of VE303 in adult subjects with 1 or more recurrences of Clostridium
difficile infection (CDI), including the current episode. VE303 or placebo capsules will be
taken orally for 14 days after completion of a course of standard of care antibiotics. The
proportion of subjects experiencing a confirmed CDI recurrence, within 8 weeks after the
first dose of study treatment, will be compared across the study arms to understand the
effectiveness of VE303 in preventing subsequent rCDI.

Approximately 146 subjects with: a history of CDI, diarrhea, a positive C. difficile toxin
stool sample test, and who have responded to standard-of-care (SOC) antibiotic treatment,
will be enrolled in the study. Participants will be randomly assigned, in a 1:1:1 ratio to 1
of 3 treatment arms (VE303 high dose, VE303 low dose, and placebo). Participants and their
doctors will not know which treatment arm is assigned.

Inclusion Criteria:

- Subjects must meet all of the following to be eligible:

1. Able and willing to provide written informed consent prior to initiation of study
treatment or of any study-specific procedures

2. Subjects with any number of recurrent CDI episodes

3. The current qualifying episode of rCDI must meet all of the following criteria:

1. Second or greater occurrence of CDI in 6 months;

2. New onset of ≥ 3 loose/unformed bowel movements within 24 hours for 2
consecutive days or > 8 loose/unformed bowel movements within 24 hours;

3. Stool sample positive for C difficile toxin by central laboratory

4. Prior to the first dose of study drug, completion of at least one
Investigator's choice of SOC antibiotic therapy for CDI with a treatment
duration of 10 to 21 days;

5. Upon completion of SOC antibiotic therapy, successful clinical response
defined as < 3 loose/unformed bowel movements within 24 hours for at least 2
consecutive days;

Exclusion Criteria:

- Subjects meeting any of the following are not eligible:

1. Subjects experiencing their first episode of CDI.

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

3. Prior administration of genetically modified and/or fecally-derived live
biotherapeutic products

4. Planned use of a proton-pump inhibitor (e.g., omeprazole, pantoprazole, etc.)
more than once per day during the 14-day study drug administration period

5. History of acute leukemia or hematopoietic stem cell transplantation or
myelosuppressive chemotherapy within 2 months prior to randomization.

6. White blood cell (WBC) count > 15,000 cells/mL, body temperature > 38.5°C, unless
resolved by the time of randomization.

7. Absolute neutrophil count of < 500 cells/mL3 on 2 consecutive occasions within 7
days prior to randomization, or sustained ANC< 1000 cells/mL3, or compromised
immune system (including corticosteroid use at doses higher than replacement
amounts within 14 days prior to randomization).

8. Current or immediate potential for mechanical ventilation or vasopressors for
hemodynamic support.

9. Major gastrointestinal surgery within 3 months prior to randomization or any
history of total colectomy or bariatric surgery that disrupts the
gastrointestinal lumen.

10. Female subject who is pregnant or breastfeeding.