3071-LB: Treatment of Obese Nonhuman Primates with an Activin E Antibody Leads to Fat-Selective Improvement in Body Composition

Introduction and Objective: Activin E (encoded by INHBE) is a liver-derived TGF-β superfamily ligand that has been implicated in regulating adipose tissue metabolism and adiposity-related phenotypes. The objective of this study was to evaluate the effects of Activin E blockade by a half-life extended antibody on body composition in obese non-human primates (NHPs), with a focus on fat mass (including visceral fat) and lean mass, and to characterize pharmacokinetics relevant to long-interval dosing. Methods: Obese NHPs received two I.V. doses of Activin E antibody (n=5) or vehicle control (n=6), at an 8-week interval. Visceral adipose tissue was quantified by magnetic resonance imaging (MRI), and total fat and lean mass (and lean mass) by dual-energy X-ray absorptiometry (DEXA). Serial blood samples were collected to measure antibody concentrations, and pharmacokinetic parameters were estimated from the linear elimination period following dose 1. Results: The Activin E antibody reduced fat mass relative to vehicle-treated controls, with a reduction of 6.7% in MRI-assessed visceral fat and a reduction of 5.2% in DEXA-assessed total fat mass following two once-every-eight-week doses. Lean mass was maintained, with a slight increase observed after treatment. Pharmacokinetic analysis following the first dose demonstrated an extended terminal half-life of 33.2 days in obese NHPs, supporting the potential of twice-yearly dosing in humans. Conclusion: The Activin E antibody produced fat-selective improvements in body composition in obese NHPs, reducing visceral and total fat mass while maintaining lean mass, and demonstrated a prolonged half-life. These findings are supportive of continued development for obesity and related cardiometabolic indications. Disclosure C. Schwartz: Employee; Current; iBio, Inc. C.W. Zour: Employee; Current; iBio, Inc. T. Hsu: Employee; Current; iBio Inc. M. Dent: Employee; Current; iBio Inc. C.A. Moore: Employee; Current; iBio Inc. A.T. Taguchi: Employee; Current; iBio Inc. H. Zhang: Employee; Current; iBio. P.J. Crutcher: None. M.B. Brenner: Employee; Current; iBio Inc.