Cullinan Therapeutics’ CD19xCD3 bispecific T-cell engager CLN-978 showed early remissions and deep B-cell depletion in Phase 1 lupus and rheumatoid arthritis studies, with a favorable safety profile and potential for expedited regulatory pathways.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Cullinan Therapeutics reported encouraging first-in-human Phase 1 results for CLN-978, an investigational CD19xCD3 bispecific T-cell engager, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Data presented at the EULAR 2026 Congress showed that a single subcutaneous target dose produced meaningful clinical improvements, including disease remissions, alongside deep B-cell depletion in patients whose disease remained active despite multiple prior therapies.
The findings come from the ongoing global OUTRACE SLE (NCT06613360) and OUTRACE RA (NCT06994143) dose-escalation studies, which are evaluating safety, pharmacodynamic activity, and preliminary efficacy across multiple dose levels.
Targeting B Cells Through T-Cell Engagement
CLN-978 redirects T cells to eliminate CD19-expressing B cells through a bispecific mechanism that links T cells to pathogenic B cells. The molecule combines high-affinity CD19 binding with an albumin-binding domain that extends half-life and supports subcutaneous administration.
B cells play a central role in lupus and RA by producing autoantibodies and driving chronic inflammation. Although biologics have improved outcomes, many patients continue to experience uncontrolled disease and long-term reliance on immunosuppression. These early findings support further evaluation of CLN-978 as a potential disease-modifying therapy, while durability of remission remains under investigation.
Dose-Dependent B-Cell Depletion and Clinical Improvement
Systemic Lupus Erythematosus: Among 14 evaluable patients, 10 (71%) achieved at least a four-point reduction in hSLEDAI after a single target dose, while five achieved DORIS remission. Investigators also reported biomarker improvements in anti-dsDNA antibodies, proteinuria, and complement markers C3 and C4. Peripheral B-cell counts declined by more than 80% in 14 of 17 patients (82%), with half of those treated at ≥20 µg achieving depletion below the limit of quantification.
Rheumatoid Arthritis: Among seven evaluable patients, five (71%) experienced improvements in disease activity and one achieved DAS28-ESR remission following a single 30 µg dose. CLN-978 also reduced RA-associated autoantibody levels without affecting protective vaccine titers. Dose-dependent B-cell depletion was observed not only in peripheral blood but also in lymph node and synovial tissue, providing direct evidence of target engagement in disease-relevant compartments. These findings place CLN-978 alongside other CD19-targeting approaches, such as CAR-T and anti-CD20/19 antibodies, but with the advantage of subcutaneous administration.
Favorable Early Safety Profile
CLN-978 was generally well tolerated at target doses up to 30 µg, including patients who received three administrations of the 20-µg target dose in the first multi-dose cohort. Most cytokine release syndrome (CRS) events were Grade 1, occurred after the initial 10 µg dose, and were manageable with standard interventions. A single Grade 3 CRS event occurred in the 45-µg cohort, prompting discontinuation of enrollment at that dose level and consideration of step-up dosing strategies. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported.
Regulatory Path Forward
Cullinan plans to present additional data from the first RA multi-dose cohort and initial clinical findings for velinotamig, its BCMAxCD3 T-cell engager, during its Immunology Day on June 10. Ongoing recruitment in the OUTRACE studies will help refine dosing strategies and determine whether early remission signals and deep tissue B-cell depletion translate into durable disease modification across broader autoimmune populations.
The ability to induce remission after a single subcutaneous dose underscores CLN-978’s potential to reshape treatment expectations in lupus and rheumatoid arthritis, positioning it among the most promising next-generation B-cell–targeted therapies.
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About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.