Tolerability, Safety, and Efficacy Study of INGAP Peptide to Treat Type 1 Diabetes Mellitus in Adults

In contrast to currently approved therapies that are directed at controlling either the
metabolic abnormalities or tissue complications of diabetes, INGAP Peptide therapy is
intended to restore ß cell mass and islet cell function. INGAP Peptide has been identified
as a substance that induces islet cell regeneration from progenitor cells resident in the
pancreas in a manner that recapitulates islet development during normal embryogenesis.

INGAP Peptide therapy has been evaluated in phase 1 and 2 studies of both T1DM and T2DM
patients (Dungan K, Diab Met Res Rev 2009; 25:558-565). Once daily injections of INGAP
Peptide for 3 months caused a statistically significant increase in C peptide secretion in
T1DM patients, and a trend towards increased C-peptide levels was seen in T2DM patients.
Glycosylated hemoglobin (HbA1c) decreased by -0.6% (p<0.0125) in T2DM patients and by -0.4%
(p<0.06) in T1DM patients.

Given the very short half-life or INGAP Peptide (i.e., <1 hour), the findings of these
earlier phase 2 studies in patients with T1DM and T2DM are very encouraging in that despite
suboptimal exposure to the drug, there was evidence of efficacy. Local injection site
reactions observed in those studies may have been due to relatively large doses of
formulations that were not optimized for tonicity and patient comfort.

This study has been designed such that the dose of INGAP Peptide will be divided across
three daily administrations using a formulation that has been improved with respect to
tonicity. The study will evaluate the safety, tolerability and C-peptide response
associated with this dosing regimen in patients with T1DM.