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

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

No impact of dexamethasone on CAR-T cell expansion in vitro and in patients with RRMM (AACR 2026) - "However, in patients with large B-cell lymphoma treated with axicabtagene ciloleucel in ZUMA-1, prophylactic steroids did not hinder CAR-T cell expansion (Cohort 6; Oluwole et al., 2021)...For these in vitro studies, surrogate versions for anito-cel (D-Domain), cilta-cel (VHH) and idecabtagene vicleucel (scFV) were generated and the impact of Dex on CAR-T cell phenotype and functionality was assessed...While Dex did not impact CAR-T cell expansion (D-Domain 4.8 vs 4.4; VHH 5.4 vs 4.3; scFV 5.3 vs 4.9 fold expansion), Dex treatment decreased IL-2 production, in vitro, making it an effective CRS treatment.While increased ALC and rapid CAR-T cell expansion within the first 28 days has been identified as a biomarker for delayed neurotoxicities, these data suggest that high dose steroids may not be an efficacious intervention for ALC restraint. Instead, Dex treatment is likely to curb proinflammatory cytokines and thus is an appropriate intervention for CRS management."

CAR T-Cell Therapy • IO biomarker • Preclinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • CD8

FDA Accepted Anito-cel BLA for the Treatment of Adult Patients with Relapsed/Refractory Multiple Myeloma (Businesswire) - "The BLA for anito-cel as a fourth-line treatment for patients with relapsed or refractory multiple myeloma is supported by results from the Phase 1 study (NCT04155749) and the pivotal Phase 2 iMMagine1 study (NCT05396885) and has been accepted by the U.S. Food and Drug Administration with an anticipated Prescription Drug User Fee Act (PDUFA) action date of December 23, 2026."

FDA filing • PDUFA • Multiple Myeloma

Gilead Sciences…announced that it has entered into a definitive agreement to acquire Arcellx (Nasdaq: ACLX) for $115 per share in cash at closing and one contingent value right of $5 per share, which represents an implied equity value of $7.8 billion payable at closing (Businesswire) - "Kite, a Gilead company, and Arcellx have an existing collaboration to co-develop and co-commercialize Arcellx’s lead pipeline candidate, anitocabtagene autoleucel (anito-cel)....The transaction was approved by both the Gilead and Arcellx Boards of Directors and is anticipated to close during the second quarter of 2026....Under the terms of the merger agreement entered into in connection with the transaction, a wholly-owned subsidiary of Gilead will commence a tender offer to acquire all of the outstanding shares of Arcellx’s common stock that Gilead does not already own for an offer price of $115 per share in cash, which represents a 68 percent premium to Arcellx’s 30-day volume-weighted average share price as of February 20, 2026..."

M&A • Multiple Myeloma

iMMagine-3: Phase 3, Randomized Study to Compare the Efficacy and Safety of Anitocabtagene Autoleucel with Standard of Care in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (EHA-EBMT-CART 2026) - P3 | "Before randomization, investigators will select the SOC regimen: pomalidomide, bortezomib, and dexamethasone; daratumumab, pomalidomide, and dexamethasone; carfilzomib, daratumumab, and dexamethasone; or carfilzomib and dexamethasone. Conclusions : iMMagine-3 is currently enrolling patients. Clinical Trial Registry : NCT06413498; https://clinicaltrials.gov/study/NCT06413498"

Clinical • P3 data • Gastrointestinal Disorder • Gene Therapies • Hematological Malignancies • Multiple Myeloma

Anitocabtagene autoleucel: FDA decision for 4L+ r/r multiple myeloma (based on iMMagine-1 trial) in H2 2026 (Gilead) - Q4 & FY2025 Results: FDA submission for 2-4L r/r multiple myeloma (based on iMMagine-3 trial) in 2027

FDA approval • FDA filing • Hematological Malignancies • Multiple Myeloma • Oncology

D-Domain Binder In Anitocabtagene Autoleucel Shows Absence of Tonic Signaling and Cross-Reactivity Profile (TCT-ASTCT-CIBMTR 2026) - "This profile differentiation may be attributed to the different BCMA-targeting binders, as current standard-of-care BCMA-directed CAR-T cell therapies either demonstrate suboptimal durability of response with idecabtagene vicleucel (ide-cel), or a risk of delayed toxicities with ciltacabtagene autoleucel (cilta-cel). Off-target activity with dual VHH CAR-T cells was seen with CLDN9, suggesting that the high avidity dual VHH binder could lead to off-tumor binding as CLDN9 is expressed in tight junctions across various tissues (Higashi et al., Sci Rep 2021). Other features of the D-Domain previously reported such as fast off-rate and lack of self-aggregation may contribute to enhanced target specificity and lack of tonic signaling, differentiating it from the dual VHH binder. Further studies are ongoing and additional data will be included if selected."

IO biomarker • Late-breaking abstract • CNS Disorders • Gastrointestinal Disorder • Hematological Malignancies • Movement Disorders • Multiple Myeloma • Parkinson's Disease • CD69 • FAS • IFNG

Anito-Cel's D-Domain Binder Has a Fast Off-Rate and Contributes to Its Differentiated Pharmacology Profile in Multiple Myeloma (TCT-ASTCT-CIBMTR 2026) - "Introduction: While BCMA directed CAR T-cell therapies have transformed the multiple myeloma (MM) treatment landscape, late-onset toxicities associated with ciltacabtagene autoleucel and idecabtagene vicleucel emphasize the need for therapies with improved safety and efficacy. Combined, these structural and functional data highlight anito-cel's unique ability to transiently engage BCMA, potentially conferring tumor killing without prolonged inflammation. These data provide a mechanistic rationale for the efficacy and safety profile observed with anito-cel in the clinic to date. Gain a deeper understanding of efficacy and safety correlates of CAR-T therapies in heme malignancies."

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

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

Arcellx Announces Late-Breaking Presentation at TANDEM Demonstrating Unique, High Target-Specificity of anito-cel’s D-Domain Binder (Businesswire) - "Dual VHH CAR-T cells show increased expression of FAS, ICAM and TRAIL, compared to D-Domain CAR-T cells, in the absence of antigen-expressing cells suggesting a tonic signaling phenotype. D-Domain CAR-T cells did not show expression of activation markers (CD69, 4-1BB) or IFNγ release, which were elevated 3-fold and 39-fold respectively, with dual VHH CAR-T cells...In this study, dual VHH CAR-T cells stimulated with CLDN9++ HEK293 cells demonstrated upregulation of activation markers, IFNγ release and target cell killing. CLDN9-induced activity was not observed with D-Domain or scFv CAR-T cells under any conditions tested."

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

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 1 Study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma. (PubMed, Blood Adv) - P1 | "Responses deepened over time and at the time of last data-cut (median follow-up 56 weeks), 8/9 (89%) of evaluable patients achieved minimal residual disease negativity. In conclusion, the findings demonstrate the safety of CART-ddBCMA cells and document durable responses to CART-ddBCMA in RRMM patients."

Journal • P1 data • CNS Disorders • Hematological Malignancies • Movement Disorders • Multiple Myeloma • Oncology • Parkinson's Disease • Plasmacytoma

Phase 1 Study Of Anitocabtagene Autoleucel For The Treatment Of Patients With Relapsed And/Or Refractory Multiple Myeloma: Results From At Least 1-year Follow-up In All Patients (IMW 2024) - "Adverse events with anito-cel, including CRS & ICANS, were manageable; no off-tumor tissue-targeted toxicity, delayed neurotoxicity nor Parkinsonian-like events were observed at time of data-cut. Efficacy analyses demonstrated 100% ORR, including 92% with VGPR or better & 76% with CR/sCR. Clinical responses were durable with an overall estimated 24-mo PFS rate of 56% with comparable responses seen in pts with 'high-risk' disease characteristics."

Clinical • P1 data • CNS 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

PHASE 1 STUDY OF ANITOCABTAGENE AUTOLEUCEL FOR THE TREATMENT OF PATIENTS WITH RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA: RESULTS FROM AT LEAST 1-YEAR FOLLOW-UP IN ALL PATIENTS (EHA 2024) - "Adverse events with anito-cel, including CRS & ICANS, were manageable; no off-tumor tissue-targeted toxicity,delayed neurotoxicity or Parkinsonian-like events were observed at time of data-cut. Efficacy analysesdemonstrated 100% ORR, including 92% with VGPR or better & 76% with CR/sCR. Clinical responses weredurable with an overall estimated 24-mo PFS rate of 56% with comparable responses seen in pts with 'high-risk' disease characteristics."

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

CART-ddBCMA for multiple myeloma: Interim results from phase I study (ESMO 2022) - P1 | "Median duration of response, PFS & OS were not evaluable at the time of data-cut because 19 of 24 evaluable pts (79%) remain in ongoing response. Conclusions CART-ddBCMA has demonstrated clinical activity, including 100% ORR & durable responses."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Phase 1 study of CART-ddBCMA in relapsed or refractory multiple myeloma. (ASCO 2022) - P1 | "Pts receive fludarabine and cyclophosphamide (30/300 mg/m2/day) days -5 to -3 and CART-ddBCMA infusion on day 0. CART-ddBCMA administration, to date, has demonstrated clinical activity, including 100% ORR with rates of CR/sCR and ≥VGPR of 67% and 88%, respectively. Durable responses beyond 18 months have been observed, including in pts with EMD."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

anitocabtagene autoleucel: FDA decision for 4L+ r/r multiple myeloma in 2026 (Gilead, 44th Annual J.P. Morgan Healthcare Conference)

FDA approval • Hematological Malignancies • Multiple Myeloma • Oncology

anitocabtagene autoleucel: FDA decision for 4L+ r/r multiple myeloma in 2026 (Gilead, 44th Annual J.P. Morgan Healthcare Conference)

FDA approval • Hematological Malignancies • Multiple Myeloma • Oncology

2025 Update of Cellular Immunotherapy for Plasma Cell Disorders. (PubMed, Turk J Haematol) - "Ide-cel and Cilta-cel are CAR-T cells directed against BCMA, having received FDA approval for RRMM based on the Phase 2 KarMMa and CARTITUDE trials, respectively...Additional anti-BCMA targeted medicines, including LCAR-B38M, completely humanized CAR-T (FHVH-T), P-BCMA-ALLO-1, ALLO-715, and anti-BCMA CAR-NK, provide promising treatment options. Moreover, the anti-CD19 Fast-CAR, designed to shorten production time, and PHE885, which possesses in-vivo proliferation capability, are regarded as very efficacious...The development of academic CAR-Ts such as ARI0002h, HBI0101, eque-cel, zevor-cel, anito-cel, and Sleeping Beauty (utilizing a non-viral vector) have importance due to their accessibility and cost-effectiveness...To overcome these issues, strategies are being implemented, including combination therapy, the incorporation of gamma-secretase inhibitors etc. In conclusion, CAR-T treatments have evolved into an effective therapy modality being anticipated to be utilized..."

Journal • Amyloidosis • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • SLAMF7

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

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