Aucatzyl (obecabtagene autoleucel) / Autolus - LARVOL DELTA

Efficacy and safety profile of obecabtagene autoleucel as a CAR T-cell therapeutic agent (ASH 2025) - "2 Conclusion - The progress in CAR T-cell therapies has transformed healthcare; however, challenges such as severe cytokine release syndrome (CRS) and related neurotoxicity have hindered their broader application. Obecabtagene autoleucel is an innovative drug."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia

A post-marketing pharmacovigilance analysis of cardiotoxicities following chimeric antigen receptor T-cell therapy using the FDA adverse event reporting system (ASH 2025) - "Therefore, a post-marketing pharmacovigilance analysis of the cardiac AEs reported to the FDAAdverse Event Reporting System (FAERS) for each CAR-T product was conducted to address thisknowledge gap. All individual case safety reports of cardiac AEs listing any of the approved CAR-T therapies[Tisagenlecleucel (Tisa-cel), Axicabtagene ciloleucel (Axi-cel), Lisocabtagene maraleucel (Liso-cel),Brexucabtagene autoleucel (Brexu-cel), Idecabtagene vicleucel (Ide-cel), Ciltacabtagene autoleucel (Cilta-cel) and Obecabtagene autoleucel (Obe-cel)] as the suspected drug were identified from the FAERSdatabase... This post-marketing pharmacovigilance analysis highlights patterns of cardiac AEs followingCAR-T therapy. Trends in AEs based on CAR-T product, age, and sex support the ongoing need forvigilance for these unique toxicities. As this study is limited by FAERS reporting bias, prospective studiesto validate these associations and elucidate the underlying mechanisms are needed,..."

Adverse events • CAR T-Cell Therapy • P4 data • Acute Coronary Syndrome • Acute Lymphocytic Leukemia • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Hypotension • Leukemia • Lymphoma • Multiple Myeloma • Myocardial Infarction • Non-Hodgkin’s Lymphoma • Thrombosis • ROR1

Chimeric antigen receptor (CAR) T-cell persistence at month 3 predicts clinical outcomes in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) treated with obecabtagene autoleucel (obe-cel) (ASH 2025) - P1/2 | "In patients who remained in remission beyond M3, including those with deep MRD-negative remissionand no post obe-cel SCT, ongoing CAR T-cell persistence at M3, measured by ddPCR, was associated withlonger EFS and OS compared with loss of persistence. Persistence status at M3 may be a marker forpredicting long-term outcomes following obe-cel treatment in patients with R/R B-ALL."

Clinical • Clinical data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia

Obecabtagene autoleucel (obe-cel), a CD19-targeting chimeric antigen receptor (CAR) T-cell therapy, in patients with severe, refractory systemic lupus erythematosus (SLE) in the Phase I CARLYSLE study: Initial safety, preliminary efficacy, pharmacokinetics, and biomarker results (ASH 2025) - P1 | "Following bridging therapy with steroids asneeded and lymphodepletion (LD; fludarabine [25 mg/m2×3], cyclophosphamide [1000 mg/m2]), obe-celwas administered to the first six pts as a single flat dose of 50×106 (±20%) CAR T-cells...Initial findings from the ongoing CARLYSLE study of obe-cel in severe, refractory SLE are promising andsuggest a favorable safety profile with obe-cel treatment, with no DLTs, pronounced CAR T-cellexpansion, and observed clinical benefit. The B-cell reconstitution profiles suggest that obe-cel mayinduce a reset of pathologic autoimmunity. Updated Phase I data with longer follow-up, and data in ptswho received 100×106 CAR T-cells will be presented."

Biomarker • Clinical • P1 data • PK/PD data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Inflammatory Arthritis • Leukemia • Lupus • Lupus Nephritis • Nephrology • Neutropenia • Renal Disease • Systemic Lupus Erythematosus • CXCL8 • IL10 • IL6 • TNFA

Safety and efficacy of carniospinal irradiation (CSI) before CAR T cell therapy in patients with acute lymphoblastic leukemia (ALL) with central nervous system (CNS) disease: A potential role for CSI beyond cell killing and into immune priming (ASH 2025) - "Background : Outcomes of patients (pts) with B-cell acute lymphoblastic leukemia (B-ALL) have improvedsignificantly with the Introduction of targeted therapies such as blinatumomab, inotuzumab, and CD19-directed CAR T cell therapies... A total of 12 patients were identified who received CSI prior to CAR T cell infusion. The time fromthe completion of CSI to infusion of CAR T cells was a median of 20 days (range, 7-67). Eleven receivedBrexu-cel, and 1 received Obe-cel."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Hematological Malignancies • Leukemia

Phase 2 study of brexu-cel in minimal residual disease positive B-cell acute lymphoblastic leukemia (ASH 2025) - P2 | "Data generated with blinatumomab inthose with MRD demonstrated an 80% conversion rate to MRD negativity...Three CAR T-cell products, tisagenlecleucel (tisa-cel), obecabtagene autoleucel (obe-cel), andbrexucabtagene autoleucel (brexu-cel) are approved for relapsed and refractory (R/R) B-ALL...Patient may receive a single dose ofvincristine with four days of dexamethasone (PH-) or continue tyrosine kinase inhibitor therapy (PH+) ifenrolling with 0.1%-4.9% blasts. Patients undergo restaging marrow prior to lymphodepletion withfludarabine (25mg/m2 x3 days) and cyclophosphamide (900mg/m2 x1 day) and cell infusion at 1x106 cellsper kg...To date 16 of60 have been infused. Accrual is ongoing with plans to extend enrollment to MD Anderson CancerCenter, Montefiore Einstein Cancer Center, and the University of Pennsylvania."

Minimal residual disease • P2 data • Residual disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia

Treatment of pediatric patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) with obecabtagene autoleucel (obe-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy: Preliminary findings from the Phase Ib/II CATULUS trial (ASH 2025) - P1 | "In the Phase I CARPALL study (NCT02443831), obe-cel (AUTO1 in CARPALL) showed promisingefficacy and a favorable safety profile in pediatric R/R B-ALL (Ghorashian et al...Eligible pts (<18 y; withR/R B-ALL that is primary refractory, in high-risk first relapse, or in second or later relapse) receivedbridging therapy at the investigator's discretion before lymphodepletion (fludarabine 4×30 mg/m2; cyclophosphamide 2×500 mg/m2), followed by a single obe-cel infusion (target dose: 1.0×106/kg CAR T-cells)...Five(25.0%) and two (10.0%) pts received prior blinatumomab or prior allogeneic stem cell transplant (SCT),respectively... Manufacture of obe-cel was successful for all pts. Obe-cel effectively expanded after a singleinfusion at a dose of 1.0×106/kg CAR T-cells. The safety profile of obe-cel in pediatric pts was consistentwith that previously reported in adults, with low rates of high-grade CRS and ICANS."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Pediatrics

CAR T cells converge on a distinct transcriptional state over time in patients with diverse hematologic malignancies (ASH 2025) - "The MYB transcription factor and its gene regulatory network appear tobe specific to this cell state. Lineage tracing using TCRs suggests that CAR T cells at peak initial expansionin patients are not clonally related to the CAR T cells that persist for months to years."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD27 • CD4 • CD8 • GZMA • GZMK • HMOX1 • IFNG

Patient characteristics, toxicity, and response after real world administration of obecabtagene autoleucel and brexucabtagene autoleucel for relapsed acute lymphoblastic leukemia: A rocca analysis (ASH 2025) - "The following prior treatment patterns were observed: median lines oftherapy before CAR-T 3 vs. 3; prior SCT 24% vs. 30%, prior blinatumomab 68% vs. 46%, prior inotuzumab45% vs. 30%.At apheresis, active disease (>5% bone marrow blasts) was present in 47% vs. 55% of obe-cel and brexu-cel pts, respectively; the remainder were in CR (with 18% vs. 22% in MRD- CR, respectively)...Rates of MRD-negative CR were high and did not differbetween cohorts. A larger sample and longer follow up are required for further analyses; we anticipate acohort of ~75 obe-cel treated pts by the annual meeting and will provide updated data."

Clinical • IO biomarker • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Cerebral Hemorrhage • Hematological Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Liver Failure • Neutropenia • KMT2A

Evaluation of commercially available chimeric antigen receptor (CAR) detection reagents for monitoring of CAR T-cell (CAR T) expansion and persistence in patients (pts) treated with obecabtagene autoleucel (obe-cel) (ASH 2025) - "Measuring obe-cel expansion and persistence using FC is feasible with commercially available Abs thatdirectly target regions of the CAR construct, such as the G4S linker. These reagents show high correlationwith anti-idiotype Abs and provide a reliable method for tracking CAR expression in pts. Use of the G4Sbinder enabled tracking of CAR T expansion kinetics and phenotypic profiles in pts with different diseaseburdens."

CAR T-Cell Therapy • Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • CD8

Renal and urinary adverse events following CAR-t therapy: A faers-based pharmacovigilance analysis (ASH 2025) - "This study aims to characterize the incidence and profileof RUAEs to inform safer CAR-T use in both hematologic and rheumatologic diseases.We extracted all reports in FAERS between January 2017 and March 2025 and analyzed patients whowere treated with FDA approved CAR-T products consisting of 5 anti-CD19 CAR-T products (Kymriah,Yescarta, Tecartus, Breyanz, Aucatyzl) and 2 anti-BCMA CAR-T CAR-T products (Abecma, Carvykti). We identified a comprehensive list of adverse renal and urinary reactions after CAR-T reported in FAERS.RUAEs are a clinically significant but underrecognized complication of CAR-T therapy. CD19-targetedproducts were associated with a broader range of renal toxicities than BCMA CAR-Ts. Our data confirmAKI is a common side effect of CAR-T, accounting for around 36% of reported RUAEs, but also showedadditional rare adverse events."

Adverse events • Acute Kidney Injury • Glomerulonephritis • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Rheumatology • ROR1

Impact of chimeric antigen receptor (CAR) product cell phenotypes on clinical outcomes following treatment with obecabtagene autoleucel (obe-cel) (ASH 2025) - P1/2 | "The OS MVAmodel included: Philadelphia chromosome status, prior inotuzumab ozogamicin (InO), bone marrowblasts at lymphodepletion, and CAR T-cell persistence (time-varying)...A higher Tcm percentage in the DP samples was an independent predictor of positive clinical outcomes,including OS, following obe-cel infusion. While the T-cell phenotype composition in the LP was weaklycorrelated with that in the DP, CD25+ HLADR+ CD4+ cells in the LP independently predicted less favorableclinical outcomes. However, other factors (e.g."

Clinical • Clinical data • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • CCR7 • CD8 • HAVCR2 • IL2RA • ISG20 • LAG3 • PD-1 • TIGIT

Obecabtagene autoleucel (obe-cel) for Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) in the Open-Label, Multi-Center, Global, Single-Arm, Phase Ib/II FELIX Study: The Impact of Bridging Therapies on CAR T-Cell Expansion and Persistence (ASH 2024) - "Here, we report the impact of BT with and without inotuzumab ozogamicin (INO) on tumor burden at lymphodepletion (LD) and pharmacokinetics (PK), including CAR T expansion and persistence...Patients received BT (chemotherapy with or without INO or TKI, single-agent INO, single-agent TKI, steroids, or rituximab) per investigator decision; use of blinatumomab as a BT agent was not permitted. Patients then underwent LD (fludarabine, 4x30mg/m2; cyclophosphamide, 2x500mg/m2), followed by obe-cel tumor-burden guided infusions on Days 1 and 10, to a target dose of 410x106 CAR T-cells...A limitation of this study is the small number of patients who received BT with INO. Further studies comparing BT with INO-containing therapies or chemotherapy are warranted."

CAR T-Cell Therapy • Clinical • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Autolus Therapeutics Presents Updated Clinical Data from the CARLYSLE Trial in Patients with Severe Refractory Systemic Lupus Erythematosus at the American Society of Hematology (ASH) Annual Meeting 2025 (The Manila Times) - "Obe-cel was well tolerated in all patients. No dose limiting toxicities (DLTs) or cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed at the 50M dose....At the 50M dose, three patients (50%) achieved CRR and five patients (83%) achieved DORIS with a median onset of 5.1 months (range: 4.9-8.9), without evidence of new disease activity at a median of 12 months of follow up (range: 8.5-16.3). All non-renal manifestations of the disease resolved by month four."

P1 data • Systemic Lupus Erythematosus

CARLYSE: Obe-cel in Adolescent [Applicable in UK Only] and Adult Severe, Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Autolus Limited | N=12 ➔ 18

Enrollment change • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Matching-Adjusted Indirect Comparison of Obecabtagene Autoleucel vs. Blinatumomab Inotuzumab Ozogamicin and Ponatinib in Relapsed or Refractory Adult B-cell Acute Lymphoblastic Leukemia (ISPOR-EU 2025) - "MAIC findings suggest that obe-cel offers clinically meaningful improvements in outcomes compared to inotuzumab, blinatumomab, and ponatinib in patients with R/R B-cell ALL."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia

Transforming the Treatment of Acute Lymphoblastic Leukemia: the Role of Bispecific Antibodies, Antibody-Drug Conjugates, and CAR T-cell Therapy. (PubMed, Curr Hematol Malig Rep) - "Tisagenlecleucel, brexucabtagene autoleucel, and obecabtagene autoleucel, are chimeric antigen receptor (CAR) T-cell therapies that improved survival compared to chemotherapy alone in patients with relapsed/refractory ALL...The combination of blinatumomab and ponatinib led to a 98% MRD negativity rates by next-generation sequencing and a 3-year overall survival of 91% without reliance on allogeneic stem cell transplantation...Expanding the use of blinatumomab, inotuzumab ozogamicin, and CAR T-cell therapy across treatment phases, together with strategic sequencing, may help overcome relapsed/refractory disease. These approaches provide renewed hope for achieving durable remissions and extending survival in patients with B-ALL."

IO biomarker • Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation

Risk Factors Associated with Sub-Optimal Outcomes Following Obecabtagene autoleucel (obe-cel) for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL): What We Have Learned from the FELIX Trial (ASH 2024) - P1/2 | "Pts received bridging therapy as appropriate and underwent lymphodepletion (LD; fludarabine, 4x30mg/m2; cyclophosphamide, 2x500mg/m2), followed by tumor burden-guided infusions on Days 1 and 10 to a target dose of 410x106 CAR T-cells...Baseline characteristics were generally similar across the two groups but a higher proportion of pts were male in the low-risk group vs the high-risk group (72% vs 47%), with increased rates of pre-treatment in low-risk pts vs high-risk pts : ≥3 prior therapies (48% vs 32%); previous allo-stem cell transplant (allo-SCT; 56% vs 41%), and previous inotuzumab ozogamicin or blinatumomab (80% vs 51%)...Pts with high-risk HT scores had consistently worse outcomes than pts with low-risk HT scores. Further studies are warranted."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRP

Obecabtagene Autoleucel (obe-cel, AUTO1) for Relapsed/Refractory Adult B-cell Acute Lymphoblastic Leukemia (R/R B-ALL): Pooled Analysis of the Ongoing FELIX Phase Ib/II Study (ASH 2023) - P1/2 | "Pts received bridging therapy as needed and lymphodepletion with fludarabine (4 × 30mg/m2) and cyclophosphamide (2 × 500mg/m2)...Baseline characteristics at screening (n=126): median age 46.5 (range 20–81) yrs; Philadelphia positive B-ALL 27%; median 2 (range 1–6) prior lines of therapy; prior blinatumomab/inotuzumab 42%/32%; median BM blast burden 37% (range 0–100) including 23% pts with EMD; prior allogeneic stem cell transplant 44%... This pooled analysis of data from all pts treated to date in the FELIX study demonstrates high rates of CR/CRi after obe-cel treatment, durable responses (median DoR not reached), and a favorable safety profile. Preliminary data suggest better outcomes in pts with low leukemia burden at screening/lymphodepletion, with higher rates of deep MRD negative complete remission, median DoR not reached at the current follow up, no Gr ≥3 CRS and one Gr ≥3 ICANS. These data support further exploration of CAR T therapy earlier in..."

P1/2 data • Retrospective data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Autolus Therapeutics plc…announces that the National Institute for Health and Care Excellence (NICE) has published draft guidance recommending AUCATZYL (obecabtagene autoleucel, or “obe-cel”)2 for use in the National Health Service (NHS) in England and Wales as a treatment option for adult patients (≥26 years) with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r B-A (The Manila Times) - "AUCATZYL will be available through routine commissioning by the NHS. Autolus intends to launch AUCATZYL in England and Wales imminently. Autolus also intends to pursue patient access to AUCATZYL through the Scottish Medical Consortium."

NICE • B Acute Lymphoblastic Leukemia

Delivery of Obecabtagene Autoleucel (obe-cel, AUTO1) for the FELIX Pivotal Study Demonstrating Robust Cell Processing, Robust Release Testing, and Reliable Logistics, Together with Readiness for Sustainable Patient (pt) Care (ASH 2023) - "The FELIX study successfully demonstrated the robust operability of obe-cel manufacturing, QC and logistics processes, meeting target V2C and V2D. All apheresis starting material successfully processed despite the multitude of constraints posed by the COVID-19 pandemic. Further optimization and improvements made during the study increased reliability, consistency and precision of the manufacturing process, and supported the development of a new obe-cel manufacturing facility with greater production capacity that aims to achieve a ≥95% manufacturing success rate with ≤15-day V2C times."

Clinical • Infectious Disease • Novel Coronavirus Disease

Long-Term Efficacy and Safety of Obecabtagene Autoleucel (obe-cel) in Adult Patients (pts) with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia ([R/R B-ALL]; Pooled Analysis from ALLCAR19 and FELIX Phase Ib Studies) or Other B-cell Malignancies (ALLCAR19 Extension Study) (ASH 2023) - P1, P1/2 | "The combined analysis of data from the ALLCAR19 and FELIX Phase Ib studies shows long-term efficacy and safety of obe-cel in pts with R/R B-ALL, with approximately one-third of pts still in remission without consolidative allo-HSCT after a median follow up of >3 years. Durable responses of >2 years were also seen in pts with R/R B-CLL and R/R B-NHL.B-cell aplasia was commonly found in long-term follow up of obe-cel recipients, but without a corresponding rise in serious late infections. Obe-cel can effect durable long-term remissions in B-cell malignancies."

P1 data • Retrospective data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Non-Hodgkin Lymphoma • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

A Case of Severe Hypophosphatemia with Renal Phosphate Wasting as a Manifestation of Hemophagocytic Lymphohistiocytosis (HLH): Role of Fibroblast Growth Factor 23 (FGF-23) (KIDNEY WEEK 2025) - "For the first time, we propose FGF23 as a potential driver of hypophosphatemia after CAR-T, specifically in the setting of HLH. In conclusion, we suggest FGF23 evaluation in this setting in patients unresponsive to standard supplementation."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Musculoskeletal Diseases • Nephrology • Orthopedics • Rare Diseases • Renal Disease • FGF23

Obecabtagene Autoleucel for Treatment of Adults with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (ASH 2024) - No abstract available

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Healthcare Resource Utilization and Costs Associated with Managing CRS and ICANS in Patients with Relapsed/Refractory Adult B-Cell Acute Lymphoblastic Leukemia Receiving Obecabtagene autoleucel (obe-cel) (ASH 2024) - P1/2 | "Medication usage (in particular tocilizumab) and hospitalization/ICU costs were key drivers of overall CRS and/or ICANS management costs (64.2% and 27.1%, respectively)...Conclusions : Grade ≥3 CRS and/or ICANS AEs are associated with increased HCRU, but these events were rare in the FELIX study. Obe-cel is designed to improve efficacy and decrease toxicity through use of a novel targeting construct and tumor burden-guided split dosing, offering a potential solution to optimize utilization of resources and reduce costs associated with CAR T-cell therapy for patients with B-ALL."

Clinical • HEOR • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Preventive care