Oblenio Bio has dosed the first patients in a Phase Ia first-in-human trial of LBL-051, a CD19×BCMA×CD3 tri-specific T-cell engager being evaluated in refractory autoimmune diseases, marking the clinical entry of an approach that aims to reset the immune system by simultaneously eliminating B cells and plasma cells.
The open-label, multicenter dose-escalation study, approved by Germany's Paul Ehrlich Institute and conducted in Europe, is enrolling patients with refractory autoimmune disease across multiple indications. The trial uses a subcutaneous dosing regimen and is assessing safety, tolerability, clinical response, and B cell and plasma cell depletion in blood and tissue, alongside select biomarkers. No clinical efficacy or safety data from the trial itself have yet been reported.
The biological rationale is supported by preclinical data presented at the 2026 European Congress of Rheumatology, in which a surrogate trispecific molecule (LBL-051-S3) administered using a step-up dosing regimen produced rapid, complete depletion of peripheral and tissue CD19+ B cells and bone marrow plasma cells in cynomolgus monkeys, without clinical cytokine release syndrome.
LBL-051 was discovered using the LeadsBody platform of China-based Nanjing Leads Biolabs Co., Ltd. (HKSE: 9887.HK), and is the sole asset of Oblenio Bio, a joint venture between Leads Biolabs and Aditum Bio. The tri-specific design, simultaneously engaging CD19 on B cells, B cell maturation antigen (BCMA) on plasma cells, and CD3 on T cells, is intended to achieve deeper lymphocyte depletion than either single-target or bispecific approaches. Several bispecific T-cell engagers targeting CD19 or BCMA individually are in clinical development for autoimmune indications, and CAR-T therapies targeting CD19 have demonstrated durable remissions in small cohorts of patients with refractory systemic lupus erythematosus and other conditions — establishing proof of concept for deep B-cell depletion as a therapeutic strategy. Whether a tri-specific off-the-shelf engager can replicate or extend those outcomes at acceptable tolerability remains to be established in the clinic. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.