Velinotamig showed renal responses in refractory lupus, with four patients achieving proteinuria below 500 mg/24 hours within 24 weeks.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Cullinan Therapeutics reported interim clinical findings from an ongoing Genrix Bio Phase 1b/2a study evaluating velinotamig (CLN-803/GR1803), an investigational B-cell maturation antigen (BCMA) × CD3 T-cell engager, in patients with active, refractory, moderate-to-severe systemic lupus erythematosus (SLE). The findings were presented at the American College of Rheumatology (ACR) Convergence 2026 on November 8, 2026, as Poster #0272.
The study is evaluating patients whose disease remains active despite at least three months of standard-of-care treatment. As of the September 8, 2026, data cutoff, 12 patients had received treatment across three multiple-dose cohorts. Among the first nine patients with at least four weeks of follow-up, eight achieved a clinically meaningful reduction of at least four points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K).
These findings indicate early clinical activity in most evaluable patients, although the small population and absence of a comparator limit conclusions about treatment efficacy.
Complete Renal Responses Within 24 Weeks
Renal outcomes represented an important finding of the study. Among seven evaluable patients with baseline urine protein excretion exceeding 500 mg/24 hours, five experienced rapid and marked reductions in proteinuria. Four of these five patients achieved the reported complete renal response threshold, with proteinuria falling below 500 mg/24 hours within 24 weeks.
Lupus nephritis is a serious manifestation of SLE that can lead to progressive kidney damage and impaired renal function. Proteinuria is an important measure of renal involvement and treatment response. The observed reductions therefore provide an encouraging early signal of improvement in renal disease activity.
However, a reduction in proteinuria alone does not establish complete restoration of kidney function. Although estimated glomerular filtration rate (eGFR) was included among the study assessments, the announcement did not provide specific eGFR outcomes. Longer follow-up will be necessary to determine whether these responses translate into sustained renal benefit.
Serological and Pharmacodynamic Responses
Beyond clinical disease-activity measures, velinotamig treatment was associated with changes in several serological and pharmacodynamic markers. These included reductions in anti-double-stranded DNA (anti-dsDNA) antibodies and blood immunoglobulin G (IgG), improvement in complement component C3, and depletion of CD19-positive B cells.
The company also reported deep and sustained reductions in pathogenic autoantibodies. These findings are relevant to SLE biology, in which autoreactive B cells and antibody-producing plasma cells contribute to autoantibody production and immune-mediated tissue injury.
Together, the changes in disease activity, serological markers and immune-cell populations provide complementary evidence of biological activity. However, these pharmacodynamic findings should not independently be interpreted as evidence of clinical remission.
Mechanism of Action and Therapeutic Rationale
Velinotamig is an investigational BCMA × CD3 T-cell engager designed to redirect cytotoxic T cells towards BCMA-expressing cells, including pathogenic, autoantibody-producing plasma cells.
Its engineered structure incorporates high-affinity binding to BCMA and lower-affinity binding to CD3. This design aims to enhance target-cell depletion while limiting nonspecific T-cell activation and associated cytokine-related toxicity.
By targeting BCMA-expressing cells, velinotamig is being investigated as an approach to reduce pathogenic autoantibody production, an important component of autoimmune disease biology.
Safety Findings and Dosing Schedule
The treatment demonstrated a favorable preliminary safety profile. No dose-limiting toxicities (DLTs), immune effector cell-associated neurotoxicity syndrome (ICANS), or Grade 3 or higher cytokine release syndrome (CRS) events were reported.
CRS occurred in two patients, with all reported events limited to Grade 1 or Grade 2 and resolving with standard management. Following modifications to the step-up dosing regimen, no Grade 2 CRS events were observed.
The open-label, multicenter, dose-escalation study evaluates safety, pharmacokinetics, pharmacodynamics and preliminary efficacy. Patients receive four intravenous doses on Days 1, 4, 8 and 29, followed by monitoring for up to 48 weeks. Assessments include adverse events, CRS, ICANS, SLEDAI-2K, 24-hour proteinuria, eGFR, autoantibodies, complement levels and B-cell depletion.
Clinical Development and Outlook
Cullinan Therapeutics holds an exclusive global licence for velinotamig from Genrix Bio, excluding Greater China, across all indications. Genrix Bio is evaluating the treatment in the SLE study in China, while Cullinan is developing subcutaneous velinotamig in a separate global Phase 1b/2a study involving patients with relapsing and refractory immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (wAIHA).
The SLE findings provide an early clinical rationale for investigating BCMA-directed T-cell engagement in autoimmune diseases associated with pathogenic autoantibodies. The combination of reduced disease activity, improvements in serological markers and proteinuria responses supports further clinical evaluation.
Nevertheless, the study remains ongoing and involves a small patient population. Larger studies and extended follow-up will be essential to establish response durability, longer-term safety and the potential clinical benefit of velinotamig in refractory SLE.
References
Velinotamig, a BCMAxCD3 T Cell Engager, Achieves Complete Renal Responses and Significantly Reduces Disease Activity in Systemic Lupus Erythematosus in Data Presented at ACR Convergence 2026. Cullinan Therapeutics, November 8, 2026
Genrix Bio Phase 1b/2a study of velinotamig in patients with refractory systemic lupus erythematosus, ClinicalTrials.gov. NCT07348055
A Phase 1b/2a Study of Velinotamig in Adults with Relapsed/Refractory ITP and wAIHA ClinicalTrials.gov ID NCT07738822
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.