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Thyroid Biology and Disease

MON-422 - AMG 732: A Novel Antibody for the Treatment of Thyroid Eye Disease (TED)

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Christopher Ward, MS: Amgen Inc.: Employee (any industry) ()
Chang-Rung Chen, Ph.D.: Amgen Inc.: Employee (any industry) ()


Purpose: AMG 732 is a next-generation insulin-like growth factor 1 receptor (IGF-1R) antibody designed for subcutaneous dosing with enhanced IGF-1R binding/inhibitory activity and extended half-life compared to teprotumumab. These attributes were assessed using in-vitro and in-vivo models.

Methods: IGF-1R binding kinetics of AMG 732 and teprotumumab were analyzed using bio-layer interferometry. The inhibitory effect of AMG 732 on the IGF-1R pathway was assessed using the NCI-H322 (H322) cell line and orbital fibroblasts (OFs) isolated from TED patients. IGF-1R degradation was determined by Western Blot in H322 cells. Pharmacokinetics of AMG 732 were evaluated in cynomolgus monkeys.

Results: AMG 732 and teprotumumab bound to human IGF-1R with KD values of 0.41 and 5.2 nM, respectively. Both antibodies fully inhibited pIGF-1R in H322 cells at saturating concentrations with IC50 values of 21 and 469 ng/mL, respectively. AMG 732 induced IGF-1R degradation in H322 cells at 100 ng/mL and inhibited pIGF-1R and pAKT in TED OFs with IC50 values of 3.8 and 5.5 pg/mL, respectively. AMG 732 exhibited a half-life in monkeys of about 22 days.

Conclusion: AMG 732 has increased binding affinity and IGF-1R inhibition compared to teprotumumab. AMG 732 shows potent IGF-1R degradation, IGF-1R pathway inhibition in TED OFs, and extended half-life in cynomolgus monkeys. These characteristics support further evaluation of AMG 732 as a subcutaneous, more convenient treatment option for patients with TED.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*