Key Takeaways

  • ETHY-001 completely blocked autoantibody-driven TSHR activation in all 34 moderate-to-severe thyroid eye disease patient serum samples tested, supporting TSHR as a promising therapeutic target for both TED and Graves' disease
  • Ethyreal Bio plans to initiate a first-in-human clinical trial of ETHY-001 in the second half of 2026

Ethyreal Bio presented preclinical data supporting its lead candidate, ETHY-001, during an oral presentation at the Endocrine Society's Annual Meeting (ENDO 2026).

ETHY-001 is an internally discovered, half-life-extended monoclonal antibody designed to block autoantibody-mediated activation of the thyroid stimulating hormone receptor (TSHR), the shared pathogenic driver of both thyroid eye disease (TED) and Graves' disease (GD). The company believes the therapy has the potential to become a differentiated, single-agent treatment for both conditions.

The presentation highlighted data demonstrating potent and highly specific binding to TSHR, complete blockade of disease-driving receptor activation across patient samples, and differentiated activity compared with insulin-like growth factor-1 receptor (IGF-1R) antagonism in preclinical TED models.

"The data presented today underscore the promise of ETHY-001 for the treatment of TED and GD," said Niranjan Kameswaran, PhD, Chief Executive Officer of Ethyreal Bio. "The depth and consistency of signaling blockade across all tested patient sera samples, combined with its differentiated activity compared to IGF-1R antagonism in TED models, reinforce our conviction in ETHY-001's product profile. We believe that ETHY-001's unique combination of potent receptor blockade, subcutaneous administration, and extended half-life has the potential to support a best-in-class, convenient, single-agent approach for both conditions. We are excited to advance ETHY-001 into the clinic this year."

Among the key findings presented, ETHY-001 demonstrated sub-nanomolar monovalent affinity for TSHR with no detectable off-target binding in a membrane protein array evaluating more than 5,000 membrane proteins. The antibody also produced complete inhibition of autoantibody-driven TSHR activation in all 34 moderate-to-severe TED patient serum samples evaluated to date, suggesting broad activity against the pathogenic antibodies that drive disease progression.

Additional studies in primary orbital fibroblasts derived from TED patients showed ETHY-001 completely inhibited secretion of both hyaluronan (HA) and interleukin-6 (IL-6) following stimulation with M22, a potent TSHR-stimulating antibody. By comparison, an IGF-1R antagonist comparator inhibited HA secretion but did not suppress IL-6 secretion, highlighting what the company described as potentially broader inhibition of disease-relevant signaling pathways through direct TSHR blockade.

Ethyreal said the collective data support advancement of ETHY-001 into clinical development for both TED and GD. The company plans to initiate a first-in-human clinical trial in the second half of 2026 to evaluate the therapy's safety, tolerability, pharmacokinetics, and pharmacodynamics.

Presentation Details

  • Title: “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”
  • Authors: Lauren Pepper, Phillip Truong, Elisa Roztocil, Gina-Eva Görtz, Mareike Horstmann, Jasvinder Paul Banga, Collyn Woeller, Anja Eckstein, Stephen Huang, Kelly Foster
  • Presenter: Kelly Foster, Ph.D., SVP, Translational Medicine, Ethyreal Bio
  • Date: Monday, June 15, 2026
  • Time / Session: 1:45 PM – 3:15 PM CT / “See through TED”