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Objectives To report initial safety, efficacy, pharmacokinetics (PK) and biomarker analyses in patients with srSLE, treated with obe-cel in the ongoing open-label CARLYSLE study ( NCT06333483).Methods Eligible patients (12–65 years) had srSLE diagnosis per 2019 EULAR/ACR criteria, SLEDAI-2K score ≥8-points at screening with ≥1 major SLE-related organ involvement and were refractory to standard therapies. Obe-cel was administered as a single flat dose of either 50×10 6 (50M) or 100×106 (100M) CAR T-cells. Primary endpoints: dose-limiting toxicities (DLTs) within 28 days of infusion, adverse event frequency. Secondary endpoints: Definition of Remission in SLE (DORIS), SLEDAI-2K, renal response, biomarkers, PK and pharmacodynamics.Results As of 04 November 2025, 13 patients were enrolled; nine adults were infused with obe-cel 50M (n=6; median follow-up: 11.4 months) or 100M (n=3; median follow-up: 3.3 months). Three adolescents were enrolled and one adult withdrew prior to infusion. Data from nine infused adults are presented. At baseline, both 50M and 100M cohorts had active srSLE (median SLEDAI-2K score: 17.0 and 18.0) and lupus nephritis was present in 6/6 and 2/3 patients, respectively.No immune effector cell-associated neurotoxicity syndrome, or Grade ≥2 cytokine release syndrome events were observed (table 1). One case of liver injury was observed (fully resolved), and was possibly related to CAR T-cell activity/concomitant medication-related toxicity (anti-infective prophylaxis) and therefore considered a DLT. In the 50M cohort: 5/6 (83.3%) patients achieved DORIS (median onset: 5.1 months); complete and partial renal response (CRR/PRR) was achieved by 3/6 (50.0%) patients (Month 1) and 1/6 (16.7%) patients (Month 7), respectively. The follow-up length was insufficient to calculate DORIS response or CRR/PRR for the 100M cohort. Clinically meaningful reductions in SLEDAI-2K (figure 1) were observed in all patients.Robust CAR T-cell expansion was observed and median time to loss of persistence was ‘≤3.0 months. All patients showed deep B-cell depletion post-infusion; >90% of reconstituted B-cells at time of recovery (median: 6.0 months) were transitional and naïve (50M cohort).Abstract LBS1:02 Figure 1Change in SLEDAI-2K score over time in adult patients infused with obe-cel at the 50M or 100M doseAbstract LBS1:02 Table 1Safety outcomes in adult patients infused with obe-cel at the 50M or 100M doseConclusions In these preliminary findings of obe-cel in srSLE, obe-cel demonstrated a favourable safety profile and clinical benefit despite severe baseline disease activity. Emerging data in the 100M cohort are consistent with the 50M cohort; evaluation is ongoing.