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This study evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of obexelimab administered intravenously in healthy volunteers (n = 48; single doses of 0.03\u201010.0\u00a0mg\/kg) and patients with rheumatoid arthritis (n = 57; 6 doses of 0.3\u201010.0\u00a0mg\/kg every 2\u00a0weeks). After single\u2010dose administration, obexelimab exhibited nonlinear PK consistent with target\u2010mediated drug disposition, with terminal elimination half\u2010life increasing from 34.4 to 102\u00a0hours and clearance decreasing from 42.4 to 16.4\u00a0mL\/day\/kg across the dose range. Multiple dosing every 2 weeks demonstrated more linear PK with low accumulation (8%\u201022% increase in area under the concentration\u2013time curve). Complete CD19 receptor occupancy occurred rapidly across doses, while CD20<jats:sup>+<\/jats:sup> B\u2010cell counts decreased to approximately 50% of baseline with dose\u2010dependent recovery (15\u201061 days after single doses). Immunomodulatory effects included partial suppression of CD86 expression and significant reduction in antigen\u2010specific antibody responses. Antidrug antibodies were detected in 44.4% and 17.5% of participants in single\u2010 and multiple\u2010dose studies, respectively, with neutralizing antibodies in 0% and 2.5%. Obexelimab was generally well\u2010tolerated, primarily mild\u2010to\u2010moderate gastrointestinal events occurring more frequently than with placebo. These results support further development of obexelimab for autoimmune disorders.<\/jats:p>","DOI":"10.1002\/cpdd.1557","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T10:00:52Z","timestamp":1749808852000},"page":"656-668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetics, Receptor Occupancy, and Pharmacodynamics of Obexelimab Following Intravenous Administration in Adult Healthy Volunteers and in Patients With Rheumatoid Arthritis"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiaodong","family":"Wang","sequence":"first","affiliation":[{"name":"Zenas BioPharma, Inc. Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minggeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Zenas BioPharma, Inc. 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