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) (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

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 (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: 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

Study Design of Two Phase 1/2 Studies to Assess Safety and Efficacy of YTB323, an Autologous CD19-Directed CAR-T Cell Therapy, in Multiple Sclerosis (ECTRIMS 2025) - P1/2 | "The RMS study (NCT06617793) is enrolling ambulatory participants (Expanded Disability Status Scale [EDSS] ⩽6.5) aged ⩾18 to ⩽60 years, RMS duration of <15 years and evidence of recent (within 1 year) breakthrough disease following ⩾6 months on HET (natalizumab, alemtuzumab, anti-CD20s). These studies will provide the scientific evidence needed for further development of YTB323 in MS."

CAR T-Cell Therapy • Clinical • P1/2 data • CNS Disorders • Fatigue • Multiple Sclerosis

Rapcabtagene Autoleucel (YTB323) Phase 2 Trial in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL): Clinical Update (SOHO 2025) - P1/2 | "Twenty-eight (44%) patients received lower-dose lymphodepletion (fludarabine/cyclophosphamide 25/250 mg/m2 for 3 days) with median follow-up of 32.8 months; 33 (52%) patients received higher-dose lymphodepletion (fludarabine/cyclophosphamide 30/500 mg/m2 for 3 days) with median follow-up of 5.4 months. Rapcabtagene auto-leucel demonstrated promising efficacy and a favorable safety profile. Despite limited patient numbers, risk-benefit analysis supports using the lower-dose lymphodepletion regimen before infusion."

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

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=18 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Jun 2028 ➔ Sep 2028

Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome

Rapcabtagene autoleucel: Regulatory submission for ANCA-associated vasculitis in 2028 or later (Novartis) - Q2 2025 Results

Regulatory • ANCA Vasculitis • Immunology

RAPCABTAGENE AUTOLEUCEL (YTB323) IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: A PHASE II TRIAL CLINICAL UPDATE (EHA 2025) - P1/2 | "At the 12.5×106 CAR positive cell dose, rapcabtagene autoleucel showed promising efficacy and a favorable safety profile. Although patient numbers were limited, risk-benefit analysis supports use of the lower-dose lymphodepletion regimen before infusion; continued assessment of long-term efficacy and safety outcomes is needed"

Clinical • P2 data • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

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=18 | Recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome

Clinical, Cellular Kinetics, Pharmacodynamics and Biomarker Data Up to 12 Months After YTB323 (Rapcabtagene Autoleucel), a Rapidly Manufactured CD19 CAR-T Therapy, From an Open-Label, Phase 1/2 Study in Severe Refractory SLE (EULAR 2025) - P1/2 | "YTB323 treatment was administered in a single dose of 12.5 × 10 6 CAR-positive viable T cells, following lymphodepletion with cyclophosphamide/fludarabine...Grade 1/2 cytokine release syndrome (CRS) was observed in 8 of 13 patients; all events resolved with (n = 7) or without (n = 1) tocilizumab treatment... YTB323 treatment resulted in improved disease activity, effective B cell depletion and recovery of naive B cell phenotype. Early clinical data suggest remarkable efficacy in the srSLE population [4], and a safety profile that is in line with that reported for CD19 CAR-T therapy in autoimmune disease [1]. These data support the continued evaluation of YTB323 in srSLE."

Biomarker • Clinical • IO biomarker • P1/2 data • PK/PD data • Ataxia • CNS Disorders • Hematological Malignancies • Infectious Disease • Inflammatory Arthritis • Lupus • Movement Disorders • Nephrology • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Systemic Lupus Erythematosus

CYTB323A12101: Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL (clinicaltrials.gov) - P1/2 | N=199 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2 • BCL6

A Study of Rapcabtagene Autoleucel in Systemic Lupus Erythematosus (SLE) Patients With Active, Refractory Lupus Nephritis (LN) (clinicaltrials.gov) - P2 | N=144 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2030 ➔ Jun 2033

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

New Novartis data at ASCO and EHA showcase momentum of pioneering portfolio with promising pipeline (Novartis Press Release) - "Novartis will present data from 60 company or investigator sponsored abstracts that have the potential to change clinical practice, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) 2025 Congress....Novartis will also highlight its US partnerships with the National Football League (NFL), Alliance for Breast Cancer Policy, and ZERO Prostate Cancer, which encourage people to make proactive decisions about their health and advance patient-centered policy solutions to help improve outcomes."

Clinical data • Castration-Resistant Prostate Cancer • Chronic Myeloid Leukemia • Diffuse Large B Cell Lymphoma • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Myelofibrosis

Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=86 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2030 ➔ Oct 2032

Trial completion date • Immunology • Scleroderma • Systemic Sclerosis

An Open-label Study to Assess the Safety, Efficacy, and Cellular Kinetics of YTB323 in Relapsing Multiple Sclerosis (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2030 ➔ Oct 2030 | Trial primary completion date: Dec 2030 ➔ Oct 2030

Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Severe Active GPA or MPA (clinicaltrials.gov) - P2 | N=126 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • ANCA Vasculitis • Rare Diseases • Vasculitis