MER3101: MAS-1 Adjuvanted Antigen-specific Immunotherapeutic for Prevention and Treatment of Type 1 Diabetes

In this four-arm (cohort) study, subjects (5 active MER3101 per arm plus 2 MAS-1 placebo)
will be randomized to receive two intramuscular doses at days 1 and 28. Subjects will receive
either MAS-1 placebo emulsion, or MAS-1 adjuvanted IBC at 33, 109 and 327 µg IBC in 0.25 mL
MAS-1 adjuvanted emulsion, followed by an additional arm to receive the maximum safe IBC dose
selected from the first 3 arms in an increased dose volume of 0.5 mL MAS-1 emulsion and 2
subjects to receive 0.5 mL MAS-1 placebo control emulsion. All groups will receive standard
intensive diabetes treatment with insulin and dietary management. The primary endpoint is to
assess the safety and tolerability of 3 doses of progressively higher IBC antigen doses of
the vaccine, and at 2 dose volumes (0.25 and 0.5 mL) of MAS-1 adjuvant emulsion at the
maximum safe dose of IBC antigen. In addition, to determine if the vaccine induces a shift
towards protection shown by increased levels of IL-4, IL-5, IL-10 and TGF-b and regulatory
changes in insulin-specific T and B cells using novel reagents to detect these unique
populations of cells in treated subjects.

Inclusion Criteria:

- Between the ages of 18 and 45 years of age who meet the ADA standard T1DM criteria and
are positive for at least 1 islet cell autoantibody.

- Type 1-diabetes mellitus diagnosed within the previous 2 years.

- Stimulated C-peptide levels ≥ 0.2 pmol/ml measured during a mixed meal tolerance test
(MMTT) conducted at least 21 days from diagnosis of diabetes and within one month (37
days) of randomization.

- At least one month from last immunization.

- Willing to comply with intensive diabetes management.

- If participant is female with reproductive potential, she must be willing to avoid
pregnancy for 18 months and have a negative pregnancy test.

- Willing to forgo routine clinical immunizations during the first 100 days after
initial study drug administration.

- HbA1c levels between 6.0 and 9.5 to be enrolled in the study.

Exclusion Criteria:

- Currently pregnant or lactating or anticipate getting pregnant for 18 months after
first injection.

- Ongoing use of medications known to influence glucose tolerance.

- Require use of systemic immunosuppressant(s).

- Any significant diabetes complications such as renal disease (proteinuria or elevated
Cr) and diabetic retinopathy.

- History of malignancies.

- Currently using non-insulin pharmaceuticals to affect glycemic control.

- Any acute or chronic complicating medical issues or abnormal clinical laboratory
results that interfere with study conduct or cause increased risk including
neurological abnormalities.

- Inability or unwillingness to comply with the provisions of this protocol.

- Active infection or positive tuberculosis test result.

- Serologic evidence of current or past HIV, Hep B, or Hep C infection.

- Known history of hypersensitivity or allergy reactions to squalane or squalene based
adjuvants or other components of the study immunogen.

- History or evidence of chronic kidney disease (serum creatinine > 1.5mg/dL).

- History of proliferative diabetic retinopathy that has not been treated with laser
therapy.

- History of neuropathy, foot ulcers, amputations, or kidney disease.