Aucatzyl (obecabtagene autoleucel) / Autolus - LARVOL DELTA

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

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

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

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), the NCCN Drugs & Biologics Compendium (NCCN Compendium), and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC) for Management of CAR T-Cell and Lymphocyte Engager-Related Toxicities, Version 1.2026. (NCCN)

NCCN guideline • Oncology

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

Efficacy and safety outcomes of obecabtagene autoleucel (obe-cel) stratified by age in patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukaemia (R/R B-ALL) (DGHO 2025) - P1/2 | "Obe-cel treatment resulted in favourable ORR and EFS with low incidence of Grade ≥3 CRS/ICANS in both age groups. Obe-cel is effective and has a positive benefit-risk profile regardless of pt age, including in older adults with R/R B-ALL."

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

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 • 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

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

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

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

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), a CD19-targeting Autologous Chimeric Antigen Receptor T-cell Therapy (CAR T) with a fast off-rate binding domain, in Patients (pts) with Severe, Refractory Systemic Lupus Erythematosus (srSLE): Preliminary Results from the Phase I CARLYSLE Study (ACR Convergence 2025) - P1 | "Following lymphodepletion with fludarabine (3×25 mg/m2) and cyclophosphamide (1x1,000 mg/m2), obe-cel was administered as a single starting target dose of 50×106 (±20%) CAR T-cells... Initial findings from the ongoing CARLYSLE study of obe-cel in srSLE show a manageable safety profile, with no DLTs, ICANS or Gr ≥2 CRS. SLEDAI-2K score reduction and clinical benefit were observed in all pts, including three pts who had a CRR. Despite the short follow up and small number of pts, initial findings are promising; further research is warranted."

CAR T-Cell Therapy • Clinical • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Infectious Disease • Inflammatory Arthritis • Leukemia • Lupus • Lupus Nephritis • Nephrology • Neutropenia • Systemic Lupus Erythematosus

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

ALLCAR19: Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia, B-cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) Using CAR T-cells to Target CD19 (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: University College, London | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Next Questions: Acute Lymphoblastic Leukemia (SOHO 2025) - "The incorporation of the CD3/CD19 bispecific T-cell engager, blinatumomab, and the anti-CD22 monoclonal antibody-drug conjugate, inotuzumab-ozogamicin, for newly diagnosed Ph-negative B-cell ALL have led to promising survival outcomes in the frontline setting for B-cell ALL...In patients at high risk of CNS relapse — such as those with high baseline white blood cell counts (>70 × 10 9) 3— high-dose cytarabine and methotrexate should be incorporated, especially if allogeneic stem cell transplant (allo-SCT) is not pursued in first complete remission (CR1)...Efforts to improve the outcomes in this subgroup include the hyper-CVAD chemotherapy backbone in combination with nelarabine and pegylated asparaginase, which results in a 3-year OS of around 74%. Furthermore, the addition of venetoclax may improve outcomes, at least in a subset of patients with early T-cell precursor (ETP) ALL...14–17 Conclusions The future of ALL treatment includes the continued optimization..."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD5 • CD7 • KMT2A

CAR-T Cell Therapy in RR B-ALL (ICBMT 2025) - "So far, three products representing autologous CAR T-cells with anti-CD19 specificity, tisagenlecleucel (tisa-cel), brexucabtagene autoleucel (brexucel) and obecabtagene autoleucel (obe-cel) have been approved for the treatment of relapsed/refractory (RR) B-ALL...Similarly, allogeneic CAR T-cells are being engineered, with the objective to simplify the logistics of the procedure. Taking into account its very high research and development potential, it can be hypothesized that, in the future, CAR T-cells will become an important component of the treatment algorithm, not necessarily restricted to RR setting, but used already in first line treatment."

CAR T-Cell Therapy • IO biomarker • CD22

FELIX Analysis Highlights Factors Tied to Improved CAR T-Cell Outcomes in ALL (Oncology News Central) - "With this update, the probability of remaining in remission at 2 years after onset was 54.1%, and the 2-year OS was 46.0%....In terms of safety, there were no new safety signals with longer follow-up. The latest analysis revealed four new infections and two new malignancies, none of which were considered related to obe-cel."

P1/2 data • B Acute Lymphoblastic Leukemia

FELIX: A Study of CD19 Targeted CAR T Cell Therapy in Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia (ALL) (clinicaltrials.gov) - P1/2 | N=153 | Active, not recruiting | Sponsor: Autolus Limited | Trial completion date: May 2025 ➔ Jun 2029 | Trial primary completion date: May 2025 ➔ Jun 2029

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase 2 Study Assessing the Clinical Activity and Safety of Obecabtagene Autoleucel as a Consolidation in Patients With Newly Diagnosed High-risk B-cell Acute Lymphocytic Leukemia (ALL) (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2025 ➔ Aug 2025

Enrollment open • Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

An Economic Model Comparing the Costs Associated with Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Among Patients Treated with Chimeric Antigen Receptor (CAR) T-Cell Therapies for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) (SOHO 2025) - P1/2 | "Objective: To estimate the cost of CRS/ICANS in patients with R/R BALL treated with obe-cel or brexucabtagene autoleucel (brexu-cel)... Obe-cel was associated with lower CRS/ICANS-related healthcare costs versus brexu-cel. These results suggest that obe-cel improves resource utilization and reduces healthcare costs versus other CAR T-cell therapies for R/R B-ALL. Funding: Autolus."

Clinical • Cytokine release syndrome • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Aucatzyl: “The committee confirmed that all issues previously identified in this application had been addressed”; Acute lymphoblastic leukemia (European Medicines Agency) - CHMP Final Minutes of the meeting on 19 - 22 May 2025: “Based on the draft opinion prepared by the CAT, the Committee adopted a positive opinion recommending the granting of a conditional marketing authorization by consensus together with the CHMP assessment report and translation timetable”

CHMP • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Oncology

Can Chimeric Antigen Receptor T-Cell Therapy Be a Definitive Treatment for Adult Relapsed/ Refractory B-Cell Acute Lymphoblastic Leukemia Without Stem Cell Transplant? Long-Term Findings and Predictors of Sustained Remission for Obecabtagene Autoleucel (SOHO 2025) - P1/2 | " Important factors identified from the UVA included: age (3), response status to first/last LOT, previous allogeneic stem-cell transplantation (SCT), and previous inotuzumab ozogamicin... Obe-cel persistence, low disease burden at lymphodepletion, and obe-cel use in earlier lines were associated with better outcomes and longer survival. These data reinforce that obe-cel persistence is important for long-term survival without additional treatments, suggesting the potential of obe-cel as a definitive treatment. Accepted for presentation at the EHA 2025 Congress (Milan, Italy; June 12-15, 2025)."

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