882-P: Eloralintide, a Selective, Long-Acting Amylin Receptor Agonist for Obesity—Phase 1 Proof of Concept

Introduction and Objective: Eloralintide (Elora; LY3841136) is a potent, long acting once weekly (QW) amylin receptor agonist under development for obesity. Unlike other amylin agonist molecules (e.g. Cagrilintide), it is designed to have minimal calcitonin activity in the clinic. Methods: The 12 wk phase 1, randomized, placebo (PBO) controlled, double blind study evaluated safety, tolerability, PK, and PD of QW SC Elora in participants with obesity or overweight. Participants n=100, mean 44 years old, 29% female, and BMI of 27-43 kg/m2 were randomized to Elora or PBO in 5 multiple ascending dose cohorts. Results: At wk 12, AUC(0-∞), AUCτ,ss, and Cmax were dose proportional with ratios of dose normalized geometric means of 1.2, 1.1, and 1.0, respectively. Mean half-life was 13.9 to 15.8 days. Common treatment emergent adverse events (TEAEs) with Elora were decreased appetite (19%), headache (12%), fatigue (11%), and COVID-19 (11%). Minimal gastrointestinal (GI) events occurred in Elora participants: diarrhea (10%), nausea (8%), and vomiting (4%). Most TEAEs were mild in severity. No deaths and 1 (4%) serious AE unrelated to Elora occurred. At wk 12 with Elora, LS mean percent change in body weight ranged from -2.6 to -11.3%. Conclusion: At 12 wks, Elora QW was well tolerated with minimal GI AEs and resulted in meaningful weight loss. A phase 2 study (NCT06230523) will further explore safety and efficacy of Elora. Disclosure S.N. Bhattachar: None. L. Tham: Employee; Eli Lilly and Company. B. Tidemann-Miller: Employee; Eli Lilly and Company. D.A. Briere: Employee; Lilly USA LLC. H. Qu: Employee; Eli Lilly and Company. A. Haupt: Employee; Lilly Diabetes. Stock/Shareholder; Lilly Diabetes. E.J. Pratt: Employee; Eli Lilly and Company. K.J. Mather: Employee; Eli Lilly and Company. Funding Eli Lilly and Company