MON-364 - NEXUS STUDY: A Phase 1 Trial to Evaluate MER511, A Fusion Protein Designed to Eliminate Circulating Pathogenic Anti-TSHR Autoantibodies for the Treatment of Graves' Disease

Background: MER511 is a fragment crystallizable region (Fc) fusion protein that contains a portion of the TSHR ectodomain and has been engineered to bind, neutralize, and clear the pathogenic anti-TSHR autoantibodies that cause Graves’ Disease (GD) through the formation of MER511:autoantibody small immune complexes and their clearance via selective FCgRIIB in LSECs. MER511 is also designed to inhibit the formation of new autoantibodies, through antigen-specific, FCgRIIB-mediated inhibition of anti-TSHR IgG producing B-cells. Data from in vitro and in vivo studies provide evidence that MER511 may directly address the underlying pathology of GD by these targeted mechanisms, allowing for restoration of normal thyroid function.

Methods: The NEXUS Study is a first-in-human, placebo-controlled, single and multiple
ascending dose study to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and immunogenicity of intravenous (i.v) and subcutaneous (s.c.) administration of MER511 in adults with a documented history of GD who are receiving a stable dose of antithyroid drug (ATD) treatment.

Results: Detailed study designs for the NEXUS Study will be presented. The primary objective for this first-in-human study is to evaluate the safety and tolerability of single and multiple IV or SC doses of MER511 in participants with GD. Secondary objectives include characterization or the PK, pharmacodynamics, and immunogenicity of MER511.

Conclusion: MER511is engineered to selectively deplete the pathogenic anti-TSHR autoantibodies that cause GD, as well as inhibit their ongoing production by pathogenic B-cells, while preserving endogenous thyroid hormone axis activity. This first-in-human NEXUS Study aims to establish initial safety, tolerability, PK, pharmacodynamics, and immunogenicity of MER511 to support further clinical development for the treatment of GD.

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