OR31-08 The FcRn Inhibitor Batoclimab Rapidly Normalizes Thyroid Function and Improves Clinical Outcomes in Graves’ Disease

Abstract Disclosure: G.J. Kahaly: The Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany receives research-associated funding from, and GJK consults for, Immunovant Inc., NY, NY, USA.​. J. Wolf: None. A. Ganz: None. M. Luffy: None. K. Albert: Employee of Immunovant, Inc. F. Ali: Employee of Immunovant, Inc. E. Lin: Employee of Immunovant, Inc. W. Macias: Employee of Immunovant, Inc.. Introduction: Thyrotropin receptor autoantibodies (TRAb) cause Graves’ hyperthyroidism and Graves’ orbitopathy (GO). Currently, there are no approved therapies targeting the underlying cause of Graves’ disease (GD). Batoclimab, a novel neonatal fragment crystallizable receptor inhibitor, reduces IgG levels, including TRAb. Objective: To describe serologic and clinical outcomes from a phase 2a, proof-of-concept, open-label, single center study evaluating batoclimab in patients with GD. Methods: Eligible patients had confirmed GD, elevated TRAb, and were biochemically hyperthyroid despite ongoing therapy with moderate-to-high dose anti-thyroid drugs (ATD) for ≥12 weeks. Patients with moderate-to-severe active GO requiring specific treatment were excluded. Batoclimab was administered via subcutaneous injection at a dose of 680 mg weekly for 12 weeks, followed by 340 mg weekly for 12 weeks. At the data cutoff, 25 patients completed Week 24 (n=23) or discontinued for non-treatment-related reasons (n=2). Results: As early as Week 1 (after a single dose of batoclimab), marked reductions from baseline in serum FT3 (mean [SD] change, -5.5 [4.9] pmol/l), FT4 (mean [SD] change,-7.7 [6.8] pmol/L), IgG (mean [SD] change, -5.4 [1.5] g/L) and TRAb levels (mean [SD] change, -6.8 [5.0] IU/L) were observed (nominal p<0.0001 vs baseline for all). By Week 2, 15/25 (60%) patients achieved FT3 and FT4 levels ≤ULN without an increase in ATD dose; this increased to 19/25 (76%) patients at Week 12, including 14/25 (56%) who were off ATD. A clinically relevant increase in mean (SD) TSH serum level, which was unmeasurable at baseline, was observed by Week 6 (mean [SD] change, 0.13 mIU/L; nominal p=0.04). The median reduction in ATD dose was 75% at Week 6. Heart rate decreased by 7 bpm by Week 3 (nominal p=0.004), and 8/18 patients receiving beta blockers at baseline were able to reduce or discontinue beta blockers by Week 9. The mean (SD) ThyPRO-39 anxiety score decreased from 34.6 (25.6) at baseline to 20.5 (22.5) at Week 12. Eighty percent of patients (20/25) had mild-to-moderate pre-existing GO at baseline. Batoclimab was associated with improvements from baseline in proptosis (mean [SD] change: Week 12, -2.0 [1.52] mm; Week 24, -2.5 [1.75]), lid aperture (Week 12, -1.4 [1.44]; Week 24, -1.7 [1.26]), and CAS in the study eye (Week 12, -1.2 [0.98]; Week 24, -1.2 [1.1]). Adverse events were mild-to-moderate, with no new safety signals. Conclusions: Batoclimab treatment rapidly normalized thyroid function and improved both cardiovascular and orbital manifestations of GD. Presentation: Monday, July 14, 2025