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Aim:To assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single, escalating subcutaneousinjections of an albumin-Exendin-4 conjugate in healthy rhesus monkeys.Methods:This study investigated single, escalating subcutaneous dosesofE2HSA ranging from 0.3 to 2.7 mg; six healthy rhesus monkeys were randomized to each dose group.Parameters of safety, includingadverse events, were assessed.The pharmacokinetic profile was assessed over 12 days.Pharmacodynamic parameters (glucose and insulinconcentrations) were measured following a step-glucose infusion (day 2) and as part of an oral glucose tolerance test (OGTT) (day 3).Results:E2HSA was generally well tolerated with some increase in gastrointestinal symptoms with escalating doses.There were dosedependent decreases in food intake.The half-life of E2HSA was approximately 53 h, with Cmax occurring between 10 and 12 h in most monkeys.Evidence of increase in glucose-dependent insulin secretion and suppressionof serum glucose excursions were observed during an OGTT at all doses compared to placebo; no episodes of hypoglycaemia occurred.Conclusions:E2HSA showed an acceptable safety profile and exhibited the expected glucagon-like peptide-1 pharmacological effects onsatiety, glucosesuppression and insulin secretion with a long acting function.