rapcabtagene autoleucel (YTB323) / Novartis - LARVOL DELTA

Exploratory Urinary Biomarkers from an Open-Label Phase 1/2 Study of Rapcabtagene Autoleucel (YTB323) Suggest Reduced Intrarenal Inflammation in Severe Refractory Systemic Lupus Erythematosus (ACR Convergence 2026) - No abstract available

Biomarker • Clinical • P1/2 data • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

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

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

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

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

Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=96 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Scleroderma • Systemic Sclerosis

Open-label, Multi-center, Phase I/II Study to Assess Safety, Disease Progression and Cellular Kinetics Following YTB323 Administration in Participants With Non-active Progressive Multiple Sclerosis (PMS) (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

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

Enrollment closed • ANCA Vasculitis • Rare Diseases • Vasculitis

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 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

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

Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Generalized Myasthenia Gravis (clinicaltrials.gov) - P1/2 | N=15 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Immunology • Myasthenia Gravis

A Study of Rapcabtagene Autoleucel in Active, Refractory Systemic Lupus Erythematosus (SLE) or Lupus Nephritis (LN) Patients (AUTOGRAPH - SLE/LN) (clinicaltrials.gov) - P2 | N=179 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

An Open-label Study to Assess the Safety, Efficacy, and Cellular Kinetics of YTB323 in Relapsing Multiple Sclerosis (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

Three deaths have forced Novartis to pause development of its CD19 CAR-T candidate in autoimmune diseases, just as Bristol Myers Squibb has halted a similar program due to immune-related adverse events (FierceBiotech) - "The Swiss pharma has temporarily halted development of its autologous CD19 CAR-T therapy, rapcabtagene autoleucel (rap-cel; YTB323), for several autoimmune diseases in immunology and neuroscience...Novartis confirmed the trials included phase 2 studies of rap-cel in systemic lupus erythematosus/lupus nephritis (CYTB323J12201), systemic sclerosis (CYTB323K12201), ANCA-associated vasculitis (CYTB323I12201) and idiopathic inflammatory myopathies (CYTB323L12201), as well as phase 1/2 studies evaluating safety, cellular kinetics and efficacy in rheumatoid arthritis and Sjogren’s disease, generalized myasthenia gravis, relapsing multiple sclerosis (MS), and non-active progressive MS (CYTB323M12101B, CYTB323O12101, CYTB323N12101 and CYTB323R12101, respectively)."

Pipeline update • Trial suspension • Lupus Nephritis • Multiple Sclerosis • Myasthenia Gravis • Rheumatoid Arthritis • Sjogren's Syndrome • Systemic Lupus Erythematosus • Vasculitis

Rapcabtagene autoleucel: Regulatory submissions for SLE/lupus nephritis in 2028 (Novartis) - Q2 2026 Results: Regulatory submission for ANCA associated vasculitis in 2029 or later

Filing • ANCA Vasculitis • Immunology • Lupus Nephritis • Systemic Lupus Erythematosus

Rapcabtagene autoleucel: Regulatory submissions for myositis, systemic sclerosis and high risk large B-cell lymphoma in 2029 or later (Novartis) - Q1 2026 Results

Filing • Immunology • Large B Cell Lymphoma • Myositis • Scleroderma

YTB323 in Treatment-Resistant Generalized Myasthenia Gravis: Sentinel Cohort Findings of an Ongoing Phase 1/2 Study (ICNMD 2026) - P1/2 | "All three participants had Grade 1 cytokine release syndrome which resolved with a single dose of tocilizumab for two participants and without intervention for the other participant. No unexpected safety signals were reported and no study stopping rules were met in this analysis of the sentinel cohort of an ongoing Phase 1/2 study of YTB323 in patients with treatment-resistant gMG. These results support continued enrollment and evaluation in the ongoing expansion cohort."

P1/2 data • CNS Disorders • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Myasthenia Gravis • Neutropenia

SAFETY, CELLULAR KINETICS AND EARLY EFFICACY OF RAPCABTAGENE AUTOLEUCEL (YTB323), A RAPIDLY MANUFACTURED AUTOLOGOUS CD19 CAR-T THERAPY, IN SEVERE, REFRACTORY AUTOIMMUNE DISEASES (EHA 2026) - P1/2, P2 | "Pts received protocol-defined lymphodepleting chemotherapy (fludarabine and cyclophosphamide), followed by rap-cel infusion. Mean reduction from BL to Month 12 in SLEDAI-2K score was 12.6 (n=10) in srSLE pts. Summary/Conclusion Rap-cel demonstrates rapid CAR-T in vivo expansion, deep B cell depletion, promising initial signs of effective B cell reset and efficacy, and a favorable safety profile in pts with IIM, dcSSc or SLE/LN."

CAR T-Cell Therapy • Clinical • CNS Disorders • Glomerulonephritis • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Lupus Nephritis • Myositis • Nephrology • Pneumococcal Infections • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Phase 2 Study of Rapcabtagene Autoleucel in Myositis (clinicaltrials.gov) - P2 | N=21 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=123 ➔ 21

Enrollment change • Enrollment closed • Immunology • Myositis

CYTB323A12101: Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL (clinicaltrials.gov) - P1/2 | N=217 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2027 ➔ May 2028

Trial completion date • 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

Novartis data at EULAR 2026 demonstrates momentum for broad immunology portfolio for complex, high unmet need diseases (GlobeNewswire) - "New Cosentyx (secukinumab) data from REPLENISH, largest ever global Phase III trial in polymyalgia rheumatica, to be highlighted in oral session; New ianalumab interim results from Sjögren’s Phase III extension study up to week 108 and Phase II data in systemic lupus erythematosus will be presented...Novartis will present new data from 31 abstracts across its industry-leading immunology portfolio at the European Alliance of Associations for Rheumatology (EULAR) Congress on June 3-6 in London, advancing scientific insight into high-burden autoimmune diseases."

Clinical data • P2 data • P3 data • Immunology • Myositis • Psoriatic Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • Systemic Sclerosis

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) - P1/2 | "Rapcabtagene autoleucel treatment was administered in a single dose of 12.5 × 106 CAR-positive viable T cells, following lymphodepletion with cyclophosphamide/fludarabine...Cytokine release syndrome (CRS) (Grade 1/2) occurred in 12/21 (57%) patients; 10/12 received tocilizumab, and no patient required transfer to the intensive care unit...Clinical data suggest remarkable efficacy of rapcabtagene autoleucel compared with previously reported outcomes of standard of care treatment in a similar srSLE patient population [6], and a safety profile that is in line with that reported for CD19 CAR-T therapy in autoimmune disease [2]. These data support the continued evaluation of rapcabtagene autoleucel in srSLE."

Biomarker • CAR T-Cell Therapy • Clinical • IO biomarker • P1/2 data • PK/PD data • CNS Disorders • Hematological Malignancies • Infectious Disease • Inflammatory Arthritis • Lupus • Pneumococcal Infections • Pneumonia • Respiratory Diseases • Systemic Lupus Erythematosus

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) - P2 | "In Cohort 1 of each study, six eligible IIM or dcSSc patients received protocol-defined lymphodepleting chemotherapy (fludarabine and cyclophosphamide), followed by a single i.v. infusion of rap-cel (12.5 x 106 cells). All patients with IIM or dcSSc discontinued and remained off all immunosuppressants after treatment with rap- cel. Conclusions Preliminary data from these safety cohorts show a favourable safety profile, CAR T-cell expansion, complete B cell depletion and promising initial efficacy (improvement in TIS [IIM], mRSS [dcSSc], and lung function [dcSSc]), in patients with severe, refractory IIM or dcSSc, supporting its continued evaluation"

CAR T-Cell Therapy • Clinical • Dermatomyositis • Hematological Disorders • Immunology • Infectious Disease • Interstitial Lung Disease • Myositis • Neutropenia • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Phase 2 Study of Rapcabtagene Autoleucel in Myositis (clinicaltrials.gov) - P2 | N=123 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jul 2030 ➔ Feb 2033 | Trial primary completion date: Jul 2029 ➔ Mar 2029

Trial completion date • Trial primary completion date • Immunology • Myositis

CYTB323A12101: Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL (clinicaltrials.gov) - P1/2 | N=217 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2028 ➔ Jun 2027

Trial completion date • 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