BZ043, a Novel Amylin Analog, in a Fixed Combination with Insulin Glargine—Nonclinical Results

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Amylinomimetics are important adjunctive drugs for treating type 1 diabetes (T1D). Here we describe the amylin analog BZ043 and its potential to be mixed with insulin glargine (GLAR) in a fixed combination (FC). The effect of BZ043 over fed glycemia, either alone or co-administered with GLAR, was investigated in rats with streptozotocin-induced diabetes (STZ). Fasted STZ rats (3 h) received a single treatment of BZ043 (0.15, 0.6 or 1.2 mg/kg), GLAR (1.5 IU/rat), or BZ043 plus GLAR (separate injections), and then had free access to food (5% glucose rich) and water. BZ043 dose-proportionally prevented meal-induced increase of glycemia and the co-treatment (0.6 or 1.2 mg/kg) with GLAR restored normoglycemia (100 mg/dL) without abrupt variations of glycemia (Figure. 1A), as further shown by comparison of the area under the blood glucose curve (Figure. 1B). Adding BZ043 to a commercial vial of GLAR at 0.1 or 0.5 mg/mL did not result in observable alteration of the average molecular radius of the samples after 24 weeks of incubation at 4 °C, as shown by dynamic light scattering (Figure. 1C). In STZ rats, BZ043 showed a prolonged anti-hyperglycemic effect and, together with GLAR, promoted a long-lasting normoglycemia, with flat variation of glycemia. While further investigation on the physicochemical stability of the combination is ongoing, our data suggest that BZ043 and glargine in a FC might improve the control of T1D in humans. Disclosure C.V.F. Nascimento: Employee; Self; Biozeus Biopharmaceutical S.A. P.G. Lacativa: Employee; Self; BIOZEUS Biopharmaceutical. F. Briand: Employee; Self; Physiogenex S.A.S.. Stock/Shareholder; Self; Physiogenex S.A.S. L.M.T. Lima: Research Support; Self; BioZeus.