The PROF Study: A Phase 1b/2 Study to Demonstrate the Safety and Efficacy of EXE-346 Live Biotherapeutic to Reduce High Bowel Movement Frequency in Patients With an Ileal Pouch-Anal Anastomosis
Published: 02/26/2026
General Information:
To evaluate whether an investigational treatment called EXE-346, a probiotic biologic drug, may help reduce bowel movement frequency in patients with an ileal pouch-anal anastomosis (IPAA or “j-pouch”).
Eligibility:
Inclusion Criteria:
- Participant is 18 years of age or older.
- Participant has had an IPAA for at least 6 months prior to screening.
- Participant has an average daily bowel movement frequency of at least 10 bowel movements recorded during screening.
Further inclusion criteria apply.
Exclusion Criteria:
- Participant is currently taking biologics or certain immune-modifying medications for IBD and is unable to stop them for the study period.
- Participant has Crohn’s-like disease of the pouch.
- Participant has advanced pouch complications such as significant strictures or fistulas.
Further exclusion criteria apply.
Study Details:
Study description/explanation of participation:
The PROF Study is evaluating EXE-346, an investigational high-dose live biotherapeutic product (a probiotic biologic drug), to see if it can safely reduce bowel movement frequency in adults who have an ileal pouch–anal anastomosis (IPAA). Participants are randomly assigned to receive either EXE-346 or placebo (a powder with no active medication) for 8 weeks, followed by the option to receive EXE-346 for an additional 8 weeks in an open-label extension. The main part of the study includes approximately 6 in-person visits over about 10 weeks (plus a follow-up call), with study activities including lab tests, stool samples, questionnaires, daily symptom tracking through an eDiary, and two pouchoscopies (a procedure like a colonoscopy for the pouch).
Description of treatment or intervention (mechanism of action):
EXE-346 is an investigational, high-dose live biotherapeutic (a probiotic biologic drug) made up of beneficial bacteria. It is designed to help restore balance to the bacteria in the gut (the microbiome), which may help reduce inflammation and improve bowel function in people with an IPAA. By supporting a healthier gut environment, EXE-346 may help lower the number of daily bowel movements.
Patient Participation Requirements:
Qualifying patients will be randomly assigned to receive either the study product (EXE-346) or placebo for 8 weeks, with the option to receive EXE-346 for an additional 8 weeks afterward. Participation includes 6 in-person study visits over approximately 10 weeks (plus a follow-up call), daily symptom tracking in an electronic diary, lab tests, stool samples, questionnaires and two pouchoscopies (at screening and Week 8). Eligible patients may need to stop certain medications before joining and keep other treatments stable during the study.
Possible risks and side effects:
The study product (EXE-346) may cause side effects. The most commonly reported side effects are bloating and/or gas, usually early on. Because EXE-346 is investigational, unknown risks are possible. Study procedures also have risks, including blood draw bruising/fainting, and pouchoscopy risks (discomfort, sedation side effects, and rare bleeding or perforation). People who are pregnant or breastfeeding cannot participate, and contraception is required during the study.
Progress to date (previous phase successes, links to abstracts, etc.):
In an earlier Phase 1b portion of the PROF study, 10 participants received EXE-346 for four weeks to evaluate safety and tolerability. The treatment was generally well tolerated, with only mild, temporary side effects reported, and participants experienced a median 23% reduction in average daily bowel movements and a 48% reduction in nighttime bowel movements. Based on these results, an independent safety monitoring board supported moving forward to the larger Phase 2 study.