Oblenio Doses First Patients in Phase 1a Trial of Trispecific T-Cell Engager LBL-051

Oblenio Bio has dosed the first patients in a phase 1a first-in-human trial of LBL-051, a trispecific T-cell engager targeting B-cell maturation antigen (BCMA), CD19, and CD3 in patients with refractory autoimmune disease, the company announced.¹ LBL-051 is designed to deplete both B cells and plasma cells to achieve a durable immune system reset and the potential for sustained drug-free remission.¹

"LBL-051 preclinical data have shown complete depletion of both B and plasma cells through dual targeting of CD19 and BCMA, with minimal cytokine release," said Ricardo Grieshaber-Bouyer, MD, PhD, professor of clinical systems immunology and head of the clinical trial unit at Friedrich-Alexander-Universität Erlangen-Nürnberg and principal investigator of the study, in a company press release.¹ "These data support LBL-051's potential to achieve full B lineage immune reset consistently, which may outperform the results from approaches using a single B cell target."

What does the phase 1a trial involve?

The open-label, multicenter phase 1a study, conducted in Germany under authorization from the Paul Ehrlich Institute using a dose-escalation design, is enrolling patients with refractory autoimmune disease across multiple indications.¹ The trial uses subcutaneous dosing and is evaluating safety, tolerability, clinical response, B-cell and plasma-cell depletion in blood and tissue, and select biomarkers.

What is the clinical rationale for this approach?

The rationale for B- and plasma-cell-depleting cell therapy in autoimmune disease builds on CD19-directed chimeric antigen receptor (CAR) T-cell studies, including a case series from the same Erlangen-Nürnberg group, which Dr Grieshaber-Bouyer co-authored, reporting that a single infusion of CD19 CAR T cells induced sustained drug-free remission in 15 patients with systemic lupus erythematosus, idiopathic inflammatory myositis, or systemic sclerosis who had inadequate responses to at least 2 prior immunosuppressive therapies.² LBL-051 is designed as an off-the-shelf T-cell engager rather than a patient-specific cell therapy, an approach the company says may allow more rapid, broader clinical evaluation than autologous CAR-T manufacturing permits.¹

What preclinical data support LBL-051, and how did Oblenio form?

LBL-051 unites 3 validated targets—BCMA, CD19, and CD3—and was developed using Leads Biolabs' LeadsBody platform under an exclusive license option Oblenio holds for global development and commercialization rights.³ In non-human primate studies presented at the 2026 EULAR Congress, step-up dosing of LBL-051 produced complete depletion of peripheral and tissue B cells and plasma cells, with emergence of immature, non-memory B cells in blood upon recovery, without cytokine release syndrome even at high exposure levels, and with dose-dependent decreases in peripheral blood immunoglobulins consistent with plasma-cell depletion.^1,4

"Our phase 1a trial design marks a significant step forward in the clinical development of T cell engagers for autoimmunity," said Tapan Maniar, MD, chief medical officer, Oblenio, in the release.¹ Gunter Assmann, MD, PhD, head of the department of rheumatology and clinical immunology at RUB University Hospital Minden, where the first patients were treated, said disease-modifying options for autoimmune disease remain limited, leaving many patients refractory to current standard of care.¹

What are the limitations?

As a first-in-human, dose-escalation study, the trial's primary purpose is establishing safety and tolerability rather than confirming efficacy, and clinical response data across the enrolled autoimmune indications have not yet been reported. Oblenio, formed by Aditum Bio and Leads Biolabs in November 2024, closed a $62 million Series B financing round in June 2026 to fund this initial clinical development.^3,4

References

1. Oblenio Bio. Oblenio announces first patients dosed in innovative phase 1a trial of LBL-051 in refractory autoimmune diseases. Press release. Published August 4, 2026. Accessed August 4, 2026. https://www.obleniobio.com/news-2026-aug4
2. Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-cell therapy in autoimmune disease—a case series with follow-up. N Engl J Med. 2024;390(8):687-700. doi:10.1056/NEJMoa2308917
3. Aditum Bio. Aditum Bio and Leads Biolabs announce the formation of Oblenio Bio to develop a tri-specific T-cell engager for autoimmune disorders. Press release. Published November 7, 2024. Accessed August 4, 2026. https://www.aditumbio.com/news/aditum-bio-and-leads-biolabs-announce-the-formation-of-oblenio-
4. Oblenio Bio. Oblenio Bio closes $62 million Series B to advance tri-specific T-cell engager LBL-051 for autoimmune diseases into clinical development. Press release. Published June 25, 2026. Accessed August 4, 2026. https://www.globenewswire.com/news-release/2026/06/25/3317342/0/en/oblenio-bio-closes-62-million-series-b-to-advance-tri-specific-t-cell-engager-lbl-051-for-autoimmune-diseases-into-clinical-development.html