2830-LB: A Single Injection of Ultra-Long-Acting GLP-1 Receptor Agonist AM-710 Produces Durable >20% Weight Loss in Obese Nonhuman Primates

Introduction and Objective: Half-life extension has historically improved tolerability, efficacy and adherence to incretins, motivating the development of longer-acting agents. AM-710 is a novel ultra-long-acting prodrug of orforglipron (OFG) that has shown months-long half-life in rodents and durable weight loss with a single injection in diet-induced obese (DIO) mice. Here, we describe the pharmacokinetics & pharmacodynamics (PK/PD) of AM-710 in DIO non-human primates (NHPs). Methods: Male DIO cynomolgus monkeys (N=4, mean weight 12.85kg) received a single 1mL SC injection of AM-710 (23 mg/kg OFG-equivalent). Animals were monitored for tolerability, plasma drug levels, and PD endpoints including food intake and body weight. Results: AM-710 was well tolerated with no observed injection site reactions. Single dose AM-710 demonstrated ultra-long-acting PK with substantial reduction in food intake (>80%) and weight loss (>20%) by Day 32, and weight loss deepened with no evidence of plateau. Conclusion: AM-710 produced deep durable weight loss in obese NHPs after one dose. AM-710 data compare favorably to reports of other incretins in obese NHPs, with greater weight loss than observed with weekly dosing of triple agonists or antibody-peptide conjugates. These data support development of AM-710 as a best-in-class GLP-1RA, with a longest-in-class profile suitable for Q3M & Q6M dosing and simplified titration. Disclosure B. Kearney: Employee; Current; Aion Medicines. B. Edagwa: None. T.J. Garnett: Stock/Shareholder; Current; Eli Lilly and Company. Board Member; Ended; Carmot Therapeutics, Inc. A. Yazdi: Employee; Current; Exavir Therapeutics, Aion Medicines.