ZP8396, currently in phase 1, is a long-acting, amylin analogue designed to improve solubility and stability and allow for co-formulation with other peptides at physiological pH. Here we present in-vivo efficacy and formulation design space of ZP8396. The acute effects on body weight (BW) loss after a single s.c. injection of ZP8396 (0,5, 3, 30, 300 nmol/kg) were measured in lean rats and monitored for 96 hours after dosing. The ability of ZP8396 (1, 3, and 15 nmol/kg, s.c., every 2nd day for 21 days) to reduce BW was tested in diet-induced obese (DIO) rats. ZP8396, at concentration supporting pharmacological relevant human doses, is stable in an aqueous formulation at neutral pH and shows no aggregation potential. ZP8396 is compatible with different physiological buffer systems and isotonic agents, commonly used for commercial medicinal products (Table 1) . Formulation of ZP8396 at physiological pH induces a significant BW loss in both lean and DIO rats vs. vehicle group. A significant BW loss was observed from start of the dosing and throughout the study period.

In conclusion, ZP8396 potently induces BW loss in lean and DIO rats and allows for aqueous stable formulation at neutral pH which provides opportunities for co-formulation with other peptides for optimal BW loss. Further preclinical characterization of co-formulation of ZP8396 with different peptides for weight management is ongoing.


J.Skarbaliene: Employee; Zealand Pharma A/S, Stock/Shareholder; Zealand Pharma A/S. J.Lundqvist: Employee; Zealand Pharma A/S. J.Villadsen: Employee; Zealand Pharma A/S.

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