A Research Trial of Aralast in New Onset Diabetes (RETAIN) - Part II

Type 1 diabetes mellitus is an autoimmune disease. This means that your immune system (the
part of your body that helps fight infections) mistakenly attacks the cells that produce
insulin (beta cells in the pancreas). As beta cells are destroyed by your immune cells,
your ability to produce insulin is decreased. Insulin helps keep blood glucose levels
normal.

People with type 1 diabetes who have the ability to produce some of their own insulin (even
though they still need to take insulin) may be able to achieve better glucose control than
people who produce no insulin at all. Better glucose control has been shown to reduce the
long-term complications of diabetes. Previous research has shown that giving medicines to
affect the immune system soon after type 1 diabetes is diagnosed may stop, delay or decrease
the destruction of beta cells, resulting in better glucose control.

In mouse models of disease, Alpha-1 Antitrypsin (AAT, Aralast NP) has been shown to reverse
new-onset diabetes and induce a state of self-tolerance. The RETAIN clinical trial is
investigating the effect of intravenous Alpha-1 antitrypsin(AAT, Aralast NP) on preserving
beta cell function and whether AAT will help slow the progression of type 1 diabetes.

Inclusion Criteria:

- Diagnosed with type 1 diabetes within the past 100 days

- Positive for at least one diabetes-related autoantibody (Anti-GAD; Anti-insulin, if
obtained within 10 days of the onset of insulin therapy; IA-2 antibody and/or ICA, or
ZnT8.)

- Peak stimulated C-peptide level > 0.2 pmol/mL following a mixed meal tolerance test
(MMTT)

Exclusion Criteria:

- Serve active disease (hepatitis, cardiac or pulmonary disease, hypertension,
immunodeficiency)

- History of any bleeding or clotting factor deficiencies, or stroke

- History of vascular disease or significant vascular abnormalities

- Positive serology exposure to HBV, HCV, HIV or toxoplasmosis

- Clinically active infection with EBV, CMV, or tuberculosis

- Prior or current use of oral, inhaled or intranasal glucocorticoids, or any
medication known to cause a significant, ongoing change in the course of T1DM or
immunologic status

- Prior treatment with AAT or hypersensitivity to AAT or human plasma-derived products

- Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides,
thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin.

- Current use of any medication known to influence glucose tolerance (e.g.,
beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine
anti-malarial drugs, lithium, niacin)

- Females who are pregnant or lactating, or are unwilling to defer pregnancy during
study participation.

- IgA deficiency

- Uncontrolled hypertension.

- Current life-threatening malignancy.

- Any condition that in the investigator's opinion may compromise study participation
or may confound the interpretation of the study results.