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Thyroid Biology and Disease

ORF49-07 - ETHY-001, a Half-Life Extended, TSHR Monoclonal Antibody Antagonist, Potently Inhibits TSHR Activation Induced by Patient Sera and M22-Induced Hyaluronan and IL-6 Secretion from TED Patient-Derived Orbital Fibroblasts

Monday, June 15, 2026
2:45 PM - 3:00 PM CT
Location: Room W184ABC
Disclosure(s):
Kelly Foster, PhD: Ethyreal Bio: Employee (any industry) ()



Introduction: Graves’ disease (GD) is a common autoimmune disorder that affects 1-2% of the adult population. The main causes of clinical burden are Graves’ hyperthyroidism and thyroid eye disease (TED), which commonly coexist within the same individual. Pathogenic stimulating autoantibodies (TSAbs) cause hyperthyroidism and TED by inappropriate hyperstimulation of the thyroid stimulating hormone receptor (TSHR) expressed in thyroid and orbital tissue, respectively. Today, there are no pharmacologic treatments for Graves’ hyperthyroidism or TED that target the causal disease process. The only approved pharmacologic treatment for TED, an IGF-1R inhibitor, is associated with high rates of on-target side effects and does not address hyperthyroidism. ETHY-001, a half-life extended monoclonal antibody antagonist of TSHR designed to directly block disease-causing TSAbs, is being developed as a novel treatment for both Graves’ hyperthyroidism and TED. Here, we characterize the in vitro potency of ETHY-001.

Methods: Monovalent affinity of ETHY-001 for TSHR was assessed by surface plasmon resonance. Functional blockade of TSHR signaling induced by M22 or sera from patients with recently manifested hyperthyroidism and TED was assessed by measuring cAMP production in cells overexpressing human TSHR. The ability to block autoantibody-induced production of hyaluronan and IL-6 was evaluated in orbital fibroblasts derived from patients with TED.

Results: ETHY-001 binds to TSHR with high affinity and high specificity, with no off-target binding observed against an array of membrane proteins. ETHY-001 fully blocks M22-induced TSHR stimulation as measured by cAMP production in TSHR-expressing cell lines. Importantly, ETHY-001 also fully blocks TSHR activation induced by polyclonal TSAbs in all tested serum samples from patients. In orbital fibroblasts, ETHY-001 showed complete blockade of M22-induced hyaluronan release as well as IL-6 release, while IGF-1R antagonism only demonstrated partial blockade.

Conclusion: Overall, these data support the potential of ETHY-001 to provide a best-in-class treatment option for the full spectrum of GD and TED patients.