Long-term remission in autoantibody-driven autoimmune disease may require eradication of pathogenic B-cell compartments followed by reconstitution of a “reset” immune repertoire. CTA313 is a B-cell–directed cell therapy incorporating proprietary edits designed to improve in vivo kinetics and therapeutic durability.

Patients received a single administration of CTA313 treatment at 3 dose levels (DLs): DL1 as 3×10⁶ CAR+ T cells/kg, DL2 as 6×10⁶ CAR+ T cells/kg, DL3 as 10×10⁶ CAR+ T cells/kg following standard dose lymphodepletion comprised of cyclophosphamide (300 mg/m², day -5 to -3) and fludarabine (30 mg/m², day -5 to -3). CTA313 cellular kinetics were assessed by qPCR (CAR transgene copies/µg DNA) longitudinally through ~Day 112. Peripheral B-cell counts were monitored through ~Day 182. B-cell phenotypes (naïve, memory, activated memory, plasmablasts) were quantified by flow cytometry at baseline and during reconstitution (e.g., Day 42 and Months 2–6). Serologic markers included total IgM and IgG, pathogenic autoantibody (anti-dsDNA), and antiviral vaccine titers (anti-Rubella) followed through ~Day 200. Clinical activity assessments include disease activity scores (SLEDAI-2K), Physician’s Global Assessment (PGA) and renal outcome measures.

As of December 25, 2025, 18 patients received CTA313 at three doses, DL1 (n=4), DL2 (n=8), DL3 (n=6). 16 (89%) patients were female, median age 36 (21-50) years, median disease duration 7 (1-17) years, and 11 (61%) had lupus nephritis. All patients had been previously treated with steroids and immunosuppressive drugs, including hydroxychloroquine (n=18), tacrolimus (n=17), mycophenolate mofetil (n=12), cyclosporine A (n=3), thalidomide (n=4), methotrexate (n=1), telitacicept (n=3) and belimumab (n=3).

To date, treatment has been well tolerated. Regarding immune related toxicities only Grade 1 cytokine release syndrome (CRS) observed in 8 (44%) of 18 patients; no neurotoxicity and GvHD were reported. Severe infection (Grade [Gr] ≥ 3) was documented in 4 pts, Gr3 herpes zoster on day 111, Gr3 febrile neutropenia on day 21, Gr3 pneumonia on days 17 and 97, and Gr5 pneumonia on days 89.

CTA313 demonstrated robust early expansion with sustained detectability over multiple months and an overall exposure profile consistent with improved pharmacokinetics (PK), greater AUC, and enhanced persistence. PK analysis revealed median peak expansion (C_max) of 253,940 copies/ug DNA by qPCR with median persistence of 42 days. Importantly, in most (67%) CAR-T persistence was measured ≥ 28 days. CTA313 treatment led to profound peripheral B-cell depletion with a prolonged nadir, followed by gradual repopulation beginning around ~Day 42 and continuing to at least ~6 months. Reconstituting B cells were initially dominated by a naïve phenotype at Day 42, with limited representation of memory/activated subsets across subsequent monthly assessments. Serologically, B-cell elimination was associated with marked, sequential reduction in circulating immunoglobulins with earlier recovery of IgM relative to IgA and IgG during reconstitution consistent with half-live. Pathogenic antibody, e.g., anti-dsDNA, declined rapidly to undetectable levels and remained suppressed through follow-up; anti-viral titers, e.g., anti-Rubella titers from prior vaccination also remained undetectable, supporting elimination of prior B-cell clones.

Eighteen patients have reached initial assessment; with a mean follow up of 6 months 100% of pts achieved SRI-4 response, 78% (14/18) achieved Lupus Low Disease Activity State (LLDAS), 50% (9/18) achieved DORIS remission. Among pts with a follow up ≥6 months, 60% (6/10) achieved DORIS remission. Importantly, 89% (16/18) of patients discontinued all immunosuppressive agents, and corticosteroids were tapered to ≤10 mg/day.

CTA313 produces deep, durable B-cell depletion followed by predominantly naïve B-cell and immunoglobin repopulation, sustained suppression of pathogenic autoantibodies, and antiviral vaccine titers—an immunologic profile consistent with an immune-reset mechanism that may enable prolonged remission in autoantibody-mediated autoimmune disease.