anitocabtagene autoleucel (CART-ddBCMA) / Arcellx, Gilead - LARVOL DELTA

The fast off-rate of anito-cel's D-Domain binder contributes to its distinctive pharmacology profile in preclinical models of multiple myeloma (ASH 2025) - "Introduction: B cell maturation antigen (BCMA) directed CAR T-cell therapies have transformed the multiple myeloma (MM) treatment landscape with idecabtagene vicleucel and ciltacabtagene autoleucel approvals in relapsed/refractory MM (RRMM). We determined that anito-cel's D-Domain binder has a faster off-rate, bound to BCMA + target cells with a distinct immune synapse architecture and demonstrated decreased cytokine production while maintaining similar cytotoxicity relative to a dual VHH BCMA CAR T. Anito-cel also maintains its ability to target BCMA variants acquired post BCMA TCEs. Combined, these structural and functional data highlight anito-cel's unique ability to transiently engage BCMA, potentially conferring tumor killing without prolonged inflammation. Emerging crystallography and epitope mapping studies will further substantiate this model."

IO biomarker • Preclinical • Gastrointestinal Disorder • Hematological Malignancies • Multiple Myeloma • CSF2 • IFNG • IL2

Single-cell transcriptomics reveal mechanisms of efficacy and toxicity in anti-BCMA CAR-T cell therapies for multiple myeloma (ASH 2025) - "Understanding the biological basis for differences inefficacy and toxicity across anti-BCMA CAR T cell therapies is key to improving outcomes.MethodsWe performed a retrospective study of patients treated with cilta-cel (n=23), ide-cel (n=22), or anito-cel(n=14) at Massachusetts General Hospital with biobanked samples available. Additionally, limited effector CAR+ T cell expansionappears to drive poor cilta-cel outcomes, underscoring the importance of CAR T cell fitness andpersistence. These findings highlight a potential therapeutic window for optimizing cilta-cel outcomesthrough early monitoring and potential opportunities for clinical interventions."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • CD8

Population differences and comparative efficacy between ciltacabtagene autoleucel (cilta-cel) from the cartitude-1 study and anitocabtagene autoleucel (anito-cel) from the iMMagine-1 study in patients with relapsed / refractory multiple myeloma (RRMM) [WITHDRAWN] (ASH 2025) - P1/2, P3 | "Introduction: Cilta-cel is a BCMA-directed CAR T-cell therapy approved in the US, the EU, and othercountries for the treatment of adult patients (pts) with lenalidomide-refractory RRMM after at least 1prior line of therapy (pLOT), including a proteasome inhibitor and an immunomodulatory drug. There were significant differences in pt characteristics between CART-1 and iMM-1,particularly the number of pLOT. This MAIC approach allowed for an indirect treatment comparison,which demonstrated that pts who received cilta-cel were more likely to achieve deeper responsescompared to those treated with anito-cel. Due to the paucity of information, PFS and OS were not part ofthe analysis."

Clinical • Hematological Malignancies • Multiple Myeloma

Phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma: Updated results from iMMagine--1 (ASH 2025) - P1, P2 | "Ongoing results from the Phase 2 iMMagine-1 trial demonstrate deep and durable efficacyand manageable safety in a heavily pre-treated, refractory 4L+ RRMM population. No delayed or non-ICANS neurotoxicities including no Parkinsonism, no cranial nerve palsies, no Guillain-Barré syndrome,and no IEC-associated enterocolitis have been observed across the Phase 1 or Phase 2 iMMagine-1studies to date. Updated data including safety and efficacy outcomes in all patients at a later data cut-offdate will be presented."

Clinical • IO biomarker • P2 data • CNS Disorders • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Movement Disorders • Multiple Myeloma • Neutropenia • Parkinson's Disease • Thrombocytopenia

Highlights of JTCC Research to be presented at ASH 2025: Multiple Myeloma (PRNewswire) - "Phase 1 study of ktx-1001, a first-in-class oral MMSET/NSD2 inhibitor, demonstrates clinical activity in relapsed/refractory multiple myeloma (ABSTRACT 25-2077); Phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma: Updated results from iMMagine--1 (ABSTRACT 25-4541); Talquetamab, a GPRC5D×CD3 bispecific antibody, in combination with pomalidomide in patients with Relapsed/Refractory multiple myeloma: Updated safety and efficacy results from the Phase 1b monumental-2 study (ABSTRACT 25-11949)."

Clinical data • Multiple Myeloma

Kite Announces New Data for Pivotal iMMagine-1 Study at ASH 2025, Highlighting Anito-cel’s Opportunity in Relapsed or Refractory Multiple Myeloma (Businesswire) - "Data from an October 7, 2025 cutoff date, including 117 patients treated with anito-cel, who were followed for a median of 15.9 months, showed an independent review committee (IRC)-assessed overall response rate (ORR) of 96%, with 74% achieving a stringent complete response or complete response (sCR or CR) per International Myeloma Working Group (IMWG) criteria....Median time to best response was 4.8 months and median time to sCR or CR was 3.2 months....The progression-free survival (PFS) rates were 82.1% at 12 months, 67.4% at 18 months and 61.7% at 24 months, meaning many patients were still alive and free from cancer progression at those timepoints. The overall survival (OS) rates showed that a significant majority of patients remained alive, with 94% at 12 months, 88% at 18 months and 83% at 24 months....Data from Investigational Agent Anito-cel Support Planned 2026 Launch in the U.S."

Launch US • P2 data • Multiple Myeloma

Additional research presented at ASH provided further insights into CAR T-cell therapies, detailing anito-cel’s mechanism and factors influencing treatment outcomes (Businesswire) - "Preclinical research (Abstract #7644) shows that anito-cel's D-Domain binder interacts with BCMA by binding and releasing quickly. Relative to a comparator CAR T-cell therapy in preclinical models, this transient interaction with cancer cells may be associated with decreased inflammation while maintaining the ability to effectively kill cancer cells. Additionally, the abstract shows anito-cel retains its ability to target cancer cells with altered BCMA expression after previous treatments, demonstrating the potential for anito-cel to maintain efficacy in patients previously exposed to BCMA-targeting therapies."

Preclinical • Multiple Myeloma

Phase 1 Study of CART-Ddbcma for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Results from at Least 1-Year Follow-up in All Patients (ASH 2023) - "Briefly, pts with RRMM who have received ≥3 prior lines of therapy were enrolled & received a single infusion of CART-ddBCMA following lymphodepletion chemotherapy (fludarabine: 30 mg/m2/d & cyclophosphamide: 300 mg/m2/d daily for 3 days). Adverse events with CART-ddBCMA, including CRS & ICANS, were manageable & no off-tumor tissue-targeted toxicity, delayed neurotoxicity, or Parkinsonian-like events were observed in the entire cohort at the time of data-cut. Ongoing efficacy results are encouraging, with 100% ORR, including 35 (92%) response of VGPR or better & 29 (76%) with CR/sCR. More importantly, clinical responses were durable with an overall estimated 18-mo PFS rate of 67% with comparable clinical responses seen in 'high-risk' patients known to have poor prognosis."

Clinical • P1 data • CNS Disorders • Hematological Malignancies • Movement Disorders • Multiple Myeloma • Oncology • Parkinson's Disease • B2M

Rare Glomerular Injury After Chimeric Antigen Receptor T Cell Therapy: Collapsing Glomerulopathy and Thrombotic Microangiopathy (KIDNEY WEEK 2025) - "Case Description A 65-year-old male with diabetes mellitus and multiple myeloma initially treated with lenalidomide, bortezomib, and dexamethasone, who achieved very good partial response followed by high dose melphalan and autologous stem cell transplant a year later. He continued maintenance lenalidomide until he was found to have recurrent disease by next-generation sequencing and started on daratumumab and carfilzomib. However, he had progression of disease, and decision was to proceed with CART-ddBCMA with Fludarabine and Cyclophosphamide lymphodepletion. Course complicated by CRS grade 1 (treated with tocilizumab and dexamethasone) and concern for IEC-associated hemophagocytic lymphohistiocytosis (IEC-HS) (treated with Anakinra and Siltuximab)...Our case suggests an additional mechanism of kidney injury through direct nephrotoxicity manifesting as collapsing glomerulopathy. Only one other case has been described in literature in which biopsy-proven collapsing..."

CAR T-Cell Therapy • IO biomarker • Acute Kidney Injury • Diabetes • Glomerulonephritis • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hypotension • Immunology • Leukemia • Metabolic Disorders • Multiple Myeloma • Nephrology • Rare Diseases • Renal Disease

Efficacy and Safety of Chimeric Antigen Receptor T-Cell Therapy in Relapsed and Refractory Multiple Myeloma – a Meta-Analysis (ASH 2024) - "We included 7 trials each of Ciltacabtagene autoleucel (cilta-cel) and Idecabtagene vicleucel (ida-cel) while 21 trials used different CAR-T cell therapies including GPRC5D, HDS269B, C-CAR088, HBI0101, CART-ddBCMA, ALLO-715, ARI0002h. This analysis has limitations with significant heterogeneity among studies. There were different CAR T-cell therapies with diverse designs of studies which limit the generalization of results."

CAR T-Cell Therapy • Retrospective data • Anemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

Phase 1 Study of Anitocabtagene Autoleucel for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM): Efficacy and Safety with 34-Month Median Follow-up (ASH 2024) - P2, P3 | "Methods : Pts with RRMM who had received ≥3 prior lines of therapy (LoT) were enrolled and received a single infusion of anito-cel following lymphodepletion chemotherapy (fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 daily for 3 days). Follow-up is continuing and updated data will be presented. Further investigations of anito-cel are ongoing in 4L+ RRMM (iMMagine-1, NCT05396885) and in earlier lines (iMMagine-3, NCT06413498)."

Clinical • P1 data • CNS Disorders • Complement-mediated Rare Disorders • Hematological Malignancies • Movement Disorders • Multiple Myeloma • Oncology • Parkinson's Disease • B2M

Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Preliminary Results from the IMMagine-1 Trial (ASH 2024) - P2 | "Following leukapheresis, optional bridging, and anito-cel manufacturing, pts received lymphodepletion chemotherapy (fludarabine 30 mg/m2/d and cyclophosphamide 300 mg/m2/d for 3 days) and a single infusion of anito-cel (target dose of 115×106 CAR+ viable T cells). Notably, no delayed neurotoxicity, cranial nerve palsies, Guillain Barre syndrome, or Parkinsonian-like symptoms were observed in the Phase 1 study or in the Phase 2 iMMagine-1 study to date. Updated data with additional follow-up will be presented."

Clinical • IO biomarker • P2 data • Anemia • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Movement Disorders • Multiple Myeloma • Neutropenia • Oncology • Parkinson's Disease • Thrombocytopenia

Gilead and Kite Showcase Continued Progress in Transforming Blood Cancer Care With New Cell Therapy Data at ASH 2025 (Businesswire) - "Updated Results from Phase 2 Pivotal iMMagine-1 Study of Anito-cel for Relapsed/Refractory Multiple Myeloma to be Presented Orally...Kite will also share new data on its next-generation bicistronic autologous CAR T-cell therapies, KITE-363 and KITE-753...A key presentation for Yescarta (axicabtagene ciloleucel) includes a joint analysis of 4-year follow-up data from ZUMA-7, which evaluated Yescarta as a second-line therapy in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) eligible for autologous stem-cell transplant (ASCT), alongside 2-year follow-up data from ALYCANTE that evaluated patients who were ASCT ineligible."

Clinical data • Acute Lymphocytic Leukemia • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Large B Cell Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma

Arcellx Provides Third Quarter 2025 Financial Results (Businesswire) - "Collaboration revenue was $4.9 million and $26.0 million for the quarters ended September 30, 2025 and 2024, respectively....This decrease was primarily driven by completion of dosing and manufacturing of anito-cel in the iMMagine-1 trial in the fourth quarter of 2024....Research and development expenses were $35.1 million and $39.2 million for the quarters ended September 30, 2025 and 2024, respectively...This decrease was primarily driven by completion of dosing and manufacturing of anito-cel in the iMMagine-1 trial in the fourth quarter of 2024."

Commercial • Multiple Myeloma

THE IMPACT OF CAR-T IN MULTIPLE MYELOMA (SIE 2025) - P3 | "In the absence of a randomized head-to-head comparison among ide-cel and cilta-cel, a retrospective, multicenter, analysis of 586 pts treated with either cilta-cel or ide-cel showed the superiority of Cilta-cel vs ide-cel in terms of response rates, PFS and OS, though associated with a more burdensome toxicity profile in terms of high-grade CRS, delayed neurotoxicity, and infections.7Anitocabtagene autoleucel (anito-cel, previously known as CART-ddBCMA) is an anti-BCMA CAR T-cell construct modeled to express a D-domain binder between the CD8 hinge-region and the transmembrane domain...Also, long-term safety data revealed a manageable profile, supporting BMS-986393 as a potential treatment for RRMM and further research (e.g., the ongoing phase II QUINTESSENTIAL study.10Interestingly, preliminary data from patients with 1-3 prior lines of therapy including a PI and an IMiD are also encouraging, with high rates of response that deepened over time and no new safety..."

Hematological Malignancies • Infectious Disease • Multiple Myeloma • CD8

…Data from the iMMagine-1 (NCT05396885) presented at the 2025 International Myeloma Society Annual Meeting in Toronto, Canada (Pharmacy Times) - "The ORR was 97% (83/86), with a complete response or stringent complete response achieved in 62% (53/86). Among patients evaluable for MRD, (n = 58), 93.1% (54/58) reached MRD negativity at a sensitivity of at least 10⁻⁵, with a median time to MRD negativity of one month (range, 1–6). By Kaplan-Meier estimates, 12-month duration of response (DoR), progression-free survival (PFS), and overall survival (OS) rates were 75.6%, 78.5%, and 96.5%, respectively."

P2 data • Multiple Myeloma

Phase 2 Registrational Study of Anitocabtagene Autoleucel for Relapsed and/or Refractory Multiple Myeloma (RRMM): Updated Results from iMMagine-1 (IMS 2025) - P2 | "Ongoing results from iMMagine-1 demonstrate deep and durable efficacy and manageable safety in a 4L+ RRMM population. No delayed or non-ICANS neurotoxicities including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome have been observed across the Phase 1 or Phase 2 iMMagine-1 studies to date. Data including efficacy and safety in all treated pts will be presented."

IO biomarker • P2 data • CNS Disorders • Hematological Disorders • Hematological Malignancies • Movement Disorders • Multiple Myeloma • Parkinson's Disease

Anitocabtagene Autoleucel: Innovation in BCMA-Targeting Therapeutics (IMS 2025) - No abstract available

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

Efficacy and Safety of Anitocabtagene Autoleucel in Participants With Newly Diagnosed Multiple Myeloma (GEM-AnitoFIRST) (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: PETHEMA Foundation | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Anitocabtagene autoleucel: Data update from P2 iMMagine-1 trial (NCT05396885) for 4L + r/r multiple myeloma in H2 2025 (Gilead) - Q2 2025 Results

P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

A Phase 1 Study of Anitocabtagene Autoleucel for the Treatment of Subjects With Non-oncology Plasma Cell-related Diseases (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Arcellx, Inc. | Initiation date: Jan 2025 ➔ Apr 2025

Trial initiation date • CNS Disorders • Immunology • Myasthenia Gravis • Oncology

Study of Anitocabtagene-autoleucel in Relapsed or Refractory Multiple Myeloma (iMMagine-1) (clinicaltrials.gov) - P2 | N=129 | Active, not recruiting | Sponsor: Kite, A Gilead Company | Recruiting ➔ Active, not recruiting | Trial completion date: May 2025 ➔ Dec 2026 | Trial primary completion date: May 2024 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Efficacy and Safety of Anitocabtagene Autoleucel in Participants With Newly Diagnosed Multiple Myeloma (GEM-AnitoFIRST) (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: PETHEMA Foundation

New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

PHASE 2 REGISTRATIONAL STUDY OF ANITOCABTAGENE AUTOLEUCEL FOR RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (RRMM): UPDATED RESULTS FROM IMMAGINE-1 (EHA 2025) - P2 | "Ongoing preliminary results from the Phase 2 iMMagine-1 trial demonstrate deep and durable efficacy and manageable safety in a high-risk 4L+ RRMM population. No delayed or non-ICANS neurotoxicities including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome have been observed across the Phase 1 or Phase 2 iMMagine-1 studies to date. Updated data including efficacy and safety in all treated pts will be presented."

IO biomarker • P2 data • Anemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Movement Disorders • Multiple Myeloma • Neutropenia • Oncology • Parkinson's Disease • Thrombocytopenia