Exploratory Placebo-Controlled Study of the Metabolic Effects of Two Medical Foods in Type 2 Diabetes

Targeting the microbiome for treating metabolic syndrome has been gaining traction with
multiple population studies demonstrating a difference between healthy individuals and
patients with metabolic syndrome. Whole Biome has identified and created two medical food
formulations (MFFs) aimed at improving metabolic syndrome via two mechanisms of action
targeting the microbiome: (1) increasing butyrate production and (2) increasing mucin
regulation.

This randomized, parallel-group, placebo-controlled, double-blinded study assesses the safety
and metabolic effects of 2 MFFs on glucose control and the generalized inflammatory state
associated with Type 2 Diabetes. The microbes have been fully characterized, certified as
Generally Recognized As Safe (GRAS) and manufactured to Good Manufacturing Practice (GMP)
standards. The target population was patients with Type 2 Diabetes who either had not been
treated with antidiabetic agents or treated with metformin +/- a sulfonylurea. Subjects were
randomized in a balanced manner to receive capsules containing placebo, WBF10 or WBF11.

Inclusion Criteria:

- Type 2 diabetes treated with diet and exercise alone or in combination with metformin
and/or sulfonylurea

- If treated with metformin and/or sulfonylurea, must have been on a stable dose of the
drug(s) for a minimum of 3 months with a stable A1c value

- If treated with diet and exercise alone, must have one of the following:

- Documented fasting plasma glucose >126 mg/dL

- A1c value ≥6.8%

- If treated with diet and exercise + metformin and/or sulfonylurea, must have a stable
A1c between 6.8% and 11.0% for 3 months prior study entry

- BMI >25 but <45 and weight stable within +/- 5% over past 3 months

- If female, must meet all the following criteria:

- Not pregnant or breastfeeding

- If of childbearing potential (including peri-menopausal women with menstruation
during past year) must practice and be willing to continue appropriate birth
control during the entire duration of the study

- Have a home freezer available for immediate freezing of stool samples

- Able to read, understand, and sign the informed consent form (ICF) and HIPAA
authorization when applicable,

- Able to communicate with the investigator, and understand and comply with protocol
requirements

Exclusion Criteria:

- Use of antibiotic, antifungal, antiparasitic, or antiviral therapy within 30 days
prior to study entry

- Planned use or antibiotic, antifungal, antiparasitic, or antiviral treatment during
the study period

- Subjects using a proton pump inhibitor must be on a stable dose that will be
maintained throughout the study period

- Present use of probiotics/nutritional supplements. (Note: Use of replacement doses of
Vitamin D, calcium supplements, and a single daily multi-vitamin tablet allowed)

- Participation in a structured weight-loss program within the past 2 months

- Change in body weight ≥5% within the past month

- Excess alcohol consumption; with an alcoholic drink defined as 12 fluid ounces of beer
(5% alcohol), 5 fluid ounces of wine (12% alcohol) or 1.5 fluid ounces of 80 proof
distilled spirits

- Women: More than 2 alcoholic drinks/day or more than 7 drinks/week

- Men: More than 3 alcoholic drinks/day or more than 10 drinks/week

- Travel outside United States within 30 days of study entry

- Planned travel outside United States during study period

- Use of an experimental drug within 30 days prior to study entry

- Known milk, peanut, tree nut, wheat, soy or shellfish allergy

- Diagnosis of a sexually transmitted disease including, but not limited to, HIV,
syphilis, herpes, gonorrhea, hepatitis A, hepatitis B, and hepatitis C

- Hospitalization during last 3 months (Same day surgery center procedures allowed)

- Active GI disease

- Gastrointestinal tract surgery (appendectomy and cholecystectomy allowed)

- Cystic fibrosis

- Any condition deemed by the investigator to disqualify subject