ODP509 Proof-of-concept, Multicenter, Open-Label Phase 2a Study of Batoclimab in Active and Moderate-to-Severe Thyroid Eye Disease

Abstract In thyroid eye disease (TED), immunoglobulin G (IgG) autoantibodies target thyrotropin receptors (TSHR) on the thyroid gland causing Graves’ disease. These TSHR-Ab also bind to the TSHR on orbital fibrocytes, inducing inflammation and hyaluronan production, resulting in extraocular muscle swelling and orbital fat expansion, causing the clinical manifestations of TED. Batoclimab (IMVT-1401) is a selective, fully human monoclonal antibody with high affinity for the IgG binding site on the neonatal Fc receptor (FcRn). Normally, the half-life of IgG is extended by FcRn-mediated recycling from lysosomal degradation. By competitively binding to the IgG binding site on FcRn, batoclimab blocks FcRn-mediated recycling of IgG, resulting in increased elimination and decreased levels of IgG. Batoclimab thus has the potential to provide clinical benefit for TED patients by reducing the level of pathogenic IgG anti-TSHR-Ab. In this open-label, multicenter, phase 2a study (NCT03922321), subjects with anti-TSHR-Ab positive, moderate-to-severe TED with a clinical activity score (CAS) ≥4 received weekly subcutaneous (SC) injections of batoclimab for six weeks (680 mg for two weeks followed by 340 mg for four weeks). Subjects were monitored for up to an additional 11 weeks. Safety and tolerability were assessed throughout the study. Pharmacodynamic changes in serum IgG and anti-TSHR-Ab were monitored weekly. Clinical efficacy was assessed weekly by response rate for proptosis (≥2 mm reduction in study eye without a deterioration in the other eye). The study eye was defined as the eye with greater proptosis at baseline. CAS response was defined as having a CAS score of 0 or 1. Seven subjects enrolled and completed this study (baseline mean [SD] age 56.7 [14.9] years, CAS 5.4 [1.1], proptosis 23.1 [3.3] mm). Serum IgG and anti-TSHR-Ab were reduced by a mean (SD) of 64.8% (17.7) and 56.7% (33.6), respectively at Week 6 compared to baseline. Similar reductions were also observed with each IgG subclass. Three of seven subjects were proptosis responders and four subjects were CAS responders. Three of seven subjects were joint responders for both proptosis and CAS. All adverse events (AEs) were mild to moderate in severity and no participant reported serious AEs or discontinuation due to AE. The most common AEs were increased lacrimation, fatigue, and dizziness (n=2 for each).There was a reversible reduction in serum albumin while on treatment which returned to normal levels in all subjects by the end of the study. In conclusion, batoclimab reduced serum IgG and especially the pathogenic anti-TSHR-Ab with an acceptable tolerability profile. Approximately half of study subjects demonstrated improvement in ophthalmologic assessments with six weeks of treatment. Together, these results support further evaluation of SC batoclimab as a therapeutic option for patients with TED. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.