rapcabtagene autoleucel (YTB323) / Novartis - LARVOL DELTA

PHASE 1 EVALUATION OF THE SAFETY AND EFFICACY OF RAPCABTAGENE AUTOLEUCEL (YTB323) IN ADULT PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (R/R B-ALL) (EBMT 2026) - "Sixteen (46%) patients were previously treated with blinatumomab and 13 (37%) patients with inotuzumab. Data from this phase 1 study suggest high cellular expansion, durable efficacy for DL2–DL4, and a manageable safety profile of rapcabtagene autoleucel in adult patients with r/r B-ALL. DL3—at which 92% of patients achieved BOR of CR/CRi by 3 months, with median DOR not reached after 22 months median follow-up— exhibited a favorable risk-benefit based on safety, cellular expansion, and encouraging efficacy"

Clinical • P1 data • Acute Lymphocytic Leukemia • Aplastic Anemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Neutropenia

Phase II Interim Results for Rapcabtagene Autoleucel (YTB323) in Patients with First-Line, High-Risk Large B-cell Lymphoma (TCT-ASTCT-CIBMTR 2026) - P1/2 | "One pt developed immune effector cell- associated hemophagocytic lymphohistiocytosis-like syndrome (Gr 2), which resolved after tocilizumab and anakinra treatment. Single-dose rapcabtagene autoleucel showed promising initial efficacy and a manageable safety profile in pts with 1L HR LBCL. Immunophenotyping and efficacy data for the final pt population with longer follow-up (≥6 mo for most pts) will be presented. Understand the initial safety and efficacy of rapcabtagene autoleucel (YTB323) in patients with large B-cell lymphoma who have received frontline chemoimmunotherapy"

Clinical • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Large B Cell Lymphoma • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Rare Diseases • Thrombocytopenia • BCL2 • BCL6

Phase 1 evaluation of the safety and efficacy of rapcabtagene autoleucel (YTB323) in adult patients with Relapsed/Refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) (ASH 2025) - P1/2 | "Sixteen pts (46%) were previously treated with blinatumomaband 13 pts (37%) with inotuzumab...CRS management includedtocilizumab (70%), siltuximab (10%), corticosteroids (40%), tocilizumab plus corticosteroids (37%), andanakinra (7%)...Seven pts received supportive measures for ICANS,including dexamethasone (5 pts, 71%) and anakinra (3 pts, 43%)... Phase 1 results with long follow-up suggest rapcabtagene autoleucel is active with highcellular expansion, durable efficacy for DL2–DL4, and a manageable safety profile in adult pts with r/r B-ALL. DL3—at which 92% of pts achieved BOR of CR/CRi by 3 mo, with median DOR not reached after 22mo median follow-up—exhibited an acceptable balance of safety, efficacy, and cellular expansion."

Clinical • P1 data • Acute Lymphocytic Leukemia • Aplastic Anemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Leukemia • Neutropenia • Rare Diseases

CLINICAL, CELLULAR KINETICS, PHARMACODYNAMICS AND BIOMARKER DATA UP TO 24 MONTHS AFTER RAPCABTAGENE AUTOLEUCEL (YTB323), A RAPIDLY MANUFACTURED CD19 CAR-T THERAPY, FROM AN OPEN-LABEL, PHASE 1/2 STUDY IN SEVERE REFRACTORY SLE (EULAR 2026) - No abstract available

Biomarker • CAR T-Cell Therapy • Clinical • IO biomarker • P1/2 data • PK/PD data • Inflammatory Arthritis

SAFETY AND EARLY EFFICACY OF RAPCABTAGENE AUTOLEUCEL (YTB323), AN AUTOLOGOUS CD19 DIRECTED CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY, IN SEVERE REFRACTORY IDIOPATHIC INFLAMMATORY MYOPATHIES AND DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS: PRELIMINARY ANALYSIS OF THE OPEN-LABEL AUTOGRAPH-IIM AND -SSC STUDIES (EULAR 2026) - No abstract available

CAR T-Cell Therapy • Clinical • Immunology • Myositis • Scleroderma • Systemic Sclerosis

Rapcabtagene Autoleucel (YTB323) for Patients with First Line High-risk Large B-cell Lymphoma (1L HR LBCL): Phase 2 Interim Results (EHA-EBMT-CART 2026) - P1/2 | "After 2 cycles of 1L therapy (R-CHOP, R-CHP-Pola, or R-EPOCH [which was required for patients with DHL]), patients were eligible if PET scan per Lugano classification showed stable disease (SD) or partial response (PR) with a Deauville score of 4/5. Additional data with longer follow-up will be available during presentation. Clinical Trial Registry : NCT03960840 (ClinicalTrial.gov)"

Clinical • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • BCL2 • BCL6

Rapcabtagene Autoleucel (YTB323) in Adult Patients with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (r/r B-ALL): Phase 1 Evaluation of the Safety and Efficacy (EHA-EBMT-CART 2026) - P1/2 | "Reuse d with permission. Clinical Trial Registry : NCT03960840 (ClinicalTrial.gov)"

Clinical • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia

CAR-T ceLL for Eradication of Active Residual Disease in LBCL (CLEAR-1 Study) (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Stanford University

New P1 trial • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • MYC

SAFETY AND EARLY EFFICACY OF RAPCABTAGENE AUTOLEUCEL, AN AUTOLOGOUS CD19- DIRECTED CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY, IN SEVERE REFRACTORY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS (SSWC 2026) - "All participants in Cohort 1 underwent lymphodepleting chemotherapy with cyclophosphamide and fluda- rabine, followed by a single intravenous infusion of rapcabtagene autoleucel, with the initial three dosed sequentially with a 28-day observation period between participants; subsequent participants were dosed in parallel. Preliminary data from Cohort 1 suggests a favorable safety profile, CAR-T cell expansion, B cell depletion and promising initial efficacy of rapcabtagene autoleucel in severe refractory dcSSc, supporting its continued evaluation."

CAR T-Cell Therapy • Clinical • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Rapcabtagene autoleucel: Regulatory submission for SLE/lupus nephritis in 2028 (Novartis) - Q4 & FY2025 Results: Regulatory submissions for myositis, systemic sclerosis and high risk large B-cell lymphoma in 2029 or later

Filing • Immunology • Large B Cell Lymphoma • Myositis • Oncology • Systemic Sclerosis

A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-Cell Stemness Shows Enhanced CAR T-Cell Efficacy in Preclinical and Early Clinical Development. (PubMed, Cancer Discov) - P1/2 | "Clinically, at doses 25-fold lower than tisagenlecleucel, YTB323 showed 1) promising overall safety (CRS [any-grade, 35%; grade ≥3, 6%], neurotoxicity [any-grade, 25%; grade ≥3, 6%]); 2) ORR of 75% and 80% for DL1 and DL2, respectively; 3) comparable CAR T-cell expansion; and 4) preservation of T-cell phenotype. Current data support continued development of YTB323 for r/r DLBCL."

CAR T-Cell Therapy • Journal • Preclinical • Diffuse Large B Cell Lymphoma • Oncology

YTB323 (Rapcabtagene Autoleucel) Demonstrates Durable Efficacy and a Manageable Safety Profile in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Phase I Study Update (ASH 2022) - P1 | "CRS was managed with tocilizumab, corticosteroids, and vasopressors in 7 (70%), 3 (30%), and 1 (10%) pts at DL2, respectively, and 1 DL3 pt (50%) received tocilizumab...ICANS management was based on dexamethasone, methylprednisolone, and anakinra in 2 (67%), 1 (33%), and 1 (33%) pts at DL2, respectively, and 1 DL4 pt (50%) received dexamethasone...At a 25-fold lower dose, rapcabtagene autoleucel expansion at DL2 was comparable by qPCR to tisagenlecleucel expansion in JULIET... Rapcabtagene autoleucel is a potent new CD19-directed CAR-T cell tx with distinct cellular kinetics, durable efficacy, and a manageable safety profile. DL2 (12.5×106) CAR+ viable T cells is the recommended dose for Phase III studies, based on the CR rate, favorable safety profile, and cellular kinetics. Updated results with expanded cellular kinetics and biomarker analyses will be presented at the meeting."

Clinical • IO biomarker • P1 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD19

Rapcabtagene Autoleucel (YTB323) in Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Phase II Trial Clinical Update (ASH 2024) - P1/2 | "28 pts (44%) received lower-dose lymphodepletion (LD) (fludarabine/cyclophosphamide [flu/cy] 25/250 mg/m2 for 3 d), median FU 32.8 mo, and 33 pts (52%) received higher-dose LD (flu/cy 30/500 mg/m2 for 3 d), median FU 5.4 mo. 2 pts (3%) received bendamustine (90 mg/m2) LD...Conclusions : At the 12.5x106 CAR+ cell dose, rapcabtagene autoleucel showed promising efficacy and a favorable safety profile. Although pt numbers were limited, risk-benefit analysis supports use of the lower-dose LD regimen before infusion; continued assessment of long-term efficacy and safety outcomes is needed."

Clinical • P2 data • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • BCL2 • BCL6 • MYC

Rapcabtagene autoleucel: Data readout from P2 AUTOGRAPH - SLE/​LN trial (NCT06581198) for SLE/lupus nephritis in 2028 or later (44th Annual J.P. Morgan Healthcare Conference, Novartis)

P2 data • Immunology • Lupus Nephritis • Systemic Lupus Erythematosus

Rapcabtagene autoleucel: Data readout from P2 AUTOGRAPH - SLE/​LN trial (NCT06581198) for SLE/lupus nephritis in 2028 or later (44th Annual J.P. Morgan Healthcare Conference, Novartis)

P2 data • Immunology • Lupus Nephritis • Systemic Lupus Erythematosus

Rapcabtagene autoleucel (YTB323) for patients with first line high-risk large B-cell lymphoma: Phase II interim results (ASH 2025) - P1/2 | "After 2 cycles of 1L therapy [R-CHOP, R-CHP-Pola, or R-EPOCH (which was required for pts with DHL)], pts were eligible if a positron emission tomography (PET)scan per Lugano classification showed stable disease (SD) or partial response (PR) with a Deauville scoreof 4 or 5...One ptwas reported by the treating investigator to have immune effector cell-associated hemophagocyticlymphohistiocytosis-like syndrome (grade 2), which resolved after treatment with tocilizumab andanakinra... A single dose of rapcabtagene autoleucel (12.5×106 CAR+ cells) showed promising initialefficacy and a manageable safety profile in pts with 1L HR LBCL. At the time of presentation, CAR-T cellimmunophenotyping data and efficacy data for the final pt population with longer follow-up (≥6 monthsfor most pts) will be available, allowing initial assessment of DOR."

Clinical • P2 data • B Cell Lymphoma • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Infectious Disease • Large B Cell Lymphoma • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • BCL6

MODULE 5: Chimeric Antigen Receptor (CAR) T-Cell Therapy and Other Novel Strategies for CLL (ASH 2024) - "This program is supported by educational grants from AstraZeneca Pharmaceuticals LP, BeiGene Ltd and Eli Lilly.Biological rationale for the investigation of CD19- directed CAR T-cell therapy for CLL Published efficacy and safety findings with lisocabtagene maraleucel (liso-cel) for R/R CLL from the Phase I/II TRANSCEND CLL 004 trial FDA approval of liso-cel for CLL previously treated with a BTK inhibitor and a Bcl-2 inhibitor; current clinical role and optimal patient selection Early findings with other CAR T-cell-based approaches (eg, liso-cel in combination with ibrutinib, brexucabtagene autoleucel, rapcabtagene autoleucel) for heavily pretreated CLL Antitumor activity observed with bispecific antibody therapy (eg, epcoritamab, NVG-111, LAVA-051) for CLL, including in patients with Richter's transformation Other promising agents and strategies under investigation for CLL"

Chronic Lymphocytic Leukemia • Oncology • Richter's Syndrome

MODULE 4: Incorporation of Chimeric Antigen Receptor (CAR) T-Cell Therapy into the Management of DLBCL (ASH 2023) - "Supported by educational grants from ADC Therapeutics, Genentech, a member of the Roche Group, Incyte Corporation, Kite, A Gilead Company, and Regeneron Pharmaceuticals Inc. Optimal timing for referral of patients with DLBCL for CAR T-cell therapy Major findings from Phase III studies with CAR T-cell therapy as second-line treatment for DLBCL FDA approvals of axi-cel and lisocabtagene maraleucel (liso-cel) as second-line therapy and identification of candidates for this strategy Long-term efficacy and safety data with axi-cel, tisagenlecleucel and liso-cel in multiregimen-relapsed DLBCL Spectrum, frequency and severity of adverse events (AEs) associated with CAR T-cell therapy for DLBCL, including cytokine release syndrome (CRS) and neurotoxicity Early results with other CAR T-cell platforms for DLBCL, such as rapcabtagene autoleucel"

Diffuse Large B Cell Lymphoma • Inflammation • Oncology

ASH 2025: Promising Phase 1 CAR-T Data for B-ALL (Mirage News) - "A phase 1 multicenter study was designed to evaluate the safety and efficacy of rapcabtagene autoleucel...in 41 previously treated patients with relapsed or refractory B-ALL who received single-infusion rapcabtagene autoleucel at targeted dose level...The best overall response of complete remission (CR) or complete remission with incomplete recovery of blood count at three months, meaning that the disease had completely disappeared or the disease had disappeared but abnormal levels of blood cells were still detected, was 70% in patients who received the lowest dose (DL1), 100% with second lowest dose (DL2), 92% with the third (DL3), and 83.3% in patients who received the highest dose (DL4)....The median duration of response (DOR) was 5.3 months for DL1 and 10.8 months for DL2, and not reached for DL3 or DL4."

P1 data • B Acute Lymphoblastic Leukemia

Real-World Outcomes of Patients with High-Grade B-Cell Lymphoma with MYC and BCL2 rearrangements Treated in the Contemporary Era (ASH 2024) - "Front-line induction therapy included R-CHOP (n=29), DA-R-EPOCH (n=29), R-CODOX-M/IVAC (n=4), Pola-R-CHP + glofitamab (n=2), R-ICE (n=2), R-HyperCVAD/MA (n=1), obinutuzumab (G)-CHOP (n=1), R-CHOP + glofitamab (n=1), R-CHOP + tafasitamab (n=1), R-CHOP + lenalidomide (n=1), DA-G-EPOCH (n=1), and R-ESHAC (n=1), as well as palliative regimens including R-mini-CHOP (n=2), PEP-C (n=1), and rituximab + prednisolone (n=1)...Nineteen patients received CAR-T therapy (8 at first relapse, 11 at subsequent relapse), including axicabtagene ciloleucel (n=10), tisagenlecleucel (n=5), rapcabtagene autoleucel (n=2), and CTX110 (n=2); the 4-year PFS and OS rates from date of CAR-T infusion were 62% and 55%, respectively. Conclusions : Our series indicates that intensification of front-line induction in patients with HGBL-MYC/BCL2-R maximizes first response and PFS, and incorporation of CNS prophylaxis into initial therapy minimizes risk of CNS relapse and improves OS. CAR-T represents a..."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

A Study to Assess Safety, Cellular Kinetics and Exploratory Efficacy of Rapcabtagene Autoleucel in Rheumatoid Arthritis and Sjogren's Disease (clinicaltrials.gov) - P1/2 | N=27 | Recruiting | Sponsor: Novartis Pharmaceuticals | N=18 ➔ 27

Enrollment change • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome

Rapcabtagene autoleucel: Regulatory submission for SLE/lupus nephritis in 2028 or later (Novartis) - Q3 2025 Results: Regulatory submissions for myositis, systemic scleroderma and high risk large B-cell lymphoma in 2028 or later

Filing • Hematological Malignancies • Immunology • Large B Cell Lymphoma • Lupus Nephritis • Myositis • Oncology • Scleroderma • Systemic Lupus Erythematosus

A Study of Rapcabtagene Autoleucel in Active, Refractory Systemic Lupus Erythematosus (SLE) Patients or Lupus Nephritis (LN) (AUTOGRAPH - SLE/LN) (clinicaltrials.gov) - P2 | N=179 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2033 ➔ Feb 2032 | Trial primary completion date: Jun 2029 ➔ Feb 2028

Trial completion date • Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Biomarker Data From an Open-Label, Phase 1/2 Study for YTB323 (Rapcabtagene Autoleucel, a Rapidly Manufactured CD19 CAR-T Therapy) Suggest Reset of the B Cell Compartment in Severe Refractory SLE (ACR Convergence 2025) - P1/2 | "Interim biomarker data from this phase 1/2 trial show complete CD19 B cell depletion and IFN pathway suppression, followed by repopulation with a naïve B cell phenotype. These findings support the concept of an immune "reset" of the B cell compartment via CD19 CAR-T therapy in srSLE."

Biomarker • Clinical • IO biomarker • P1/2 data • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD27

Novartis showcases significant immunology advancements in ACR congress with new data in complex autoimmune diseases (Novartis Press Release) - "Data to be presented include late-breaking pivotal Phase III results from the replicate NEPTUNUS-1 and NEPTUNUS-2 trials evaluating ianalumab in Sjögren’s disease. New biomarker data from an ongoing Phase 1/2 study of rapcabtagene autoleucel in severe refractory systemic lupus erythematosus will also be presented, along with Cosentyx data in multiple rheumatology indications."

Clinical data • Psoriatic Arthritis • Sjogren's Syndrome • Systemic Lupus Erythematosus