In vivo CD19 CAR T-cell therapy (STR-P004) to induce remission in patients with autoimmune diseases (AID).

Abstract

e14519 Background: Conventional CAR-T therapy is costly and complex. STARNA's STR-P004 utilizes a proprietary LNP platform to deliver anti-CD19 CAR mRNA intravenously, generating functional CAR-T cells directly in vivo, thereby improving accessibility. Methods: STR-P004 integrates optimized mRNA into tissue-targeted LNPs. Its formulation includes a lead ionizable lipid conjugated with a CD8-targeting ligand. Using a TITE-BOIN12 design, AID patients received escalating doses (0.03-0.1mg/kg), up to 8 infusions. Safety and efficacy were assessed. Results: Preclinical studies showed efficient CAR expression on CD8⁺T cells, deep B-cell depletion, and prolonged survival with a favorable safety profile in primates(transient liver enzyme elevations and cytokine release).No anti-PEG antibodies were detected. Between Sep,1,2025 and Jan,20,2026, 3 AID patients (SLE-ITP, APS-ITP, SLE nephritis) were enrolled and each received 8 doses. No DLT or ICANS occurred. All 3 patients developed mild, transient grade 1 CRS after the first 2 infusions, with transient elevations in IL-6 (median 2.63pg/mL, range < 1.5–329.2), ALT (46U/L, 15–173), AST (28 U/L, 13–161), and creatinine (63.9μmol/L, 49.3–96.7). Transient neutrophil increase and lymphocyte decrease were observed, none requiring intervention. No ADA or HAMA was detected. Peripheral B cells dropped within 12h and cleared fully by 72-156h (lasting 3-12 days). CART cells expanded with each dose, peaking at 12h (median 48.84 cells/μL, range 0-851.57), accounting for 3.07% of CD3⁺T cells. The peak CD3⁺CD8⁺CAR⁺/CD8⁺ratio reached 56.96%. dsDNA antibodies initially decreased but rebounded in all patients (values: 11.34→9.41→104.36; 0.89→5.76→11.92; 57.03→11.03→37.07 IU/mL). Both ITP patients had initial platelet increases post-dose 3 (29→70; 41→57*10⁹/L), which later declined (51;5*10⁹/L). The lupus nephritis patient achieved urinary protein negativity (504→91.12→90.09 mg/24h), with rapid improvement in arthritis, rash, and alopecia. SLEDAI-2000 scores were 14, 2, 11 and PGA scores 3, 1, 1.5 at baseline, 1 month, and 1.5 months, respectively. The SLE-ITP patient later developed proteinuria (280→538 mg/24h), with SLEDAI-2000 rising from 5→9→11 and PGA from 1→1.5→2 over 3 months. Single-cell sequencing confirmed rapid clearance of CD19⁺ B cells and elimination of pathogenic B-cell clones. CAR-T cells, especially CD8⁺ subsets, expanded robustly without exhaustion. Non-integrated CAR mRNA led to limited persistence, reducing long-term overactivation risks. The therapy also spared bone marrow function and promoted juvenile neutrophil release with attenuated inflammation, lowering infection and CRS risks. Conclusions: STR-P004, an off-the-shelf, repeatable therapy, demonstrated favorable safety and initial efficacy in AID, particularly for patients requiring continuous immunosuppression. Clinical trial information: NCT07143617 .