LB2102 / Legend Biotech, Novartis - LARVOL DELTA

Safety and Efficacy of DLL3 CAR-T Cells Armored With dnTGFBR2 in a Patient With Recurrent Small-Cell Lung Cancer (IASLC-WCLC 2025) - "Methods : The patient (51 years old, female) had SCLC progression, symptomatic brain metastases, and a lung lesion approximately 8 months after starting platinum-based combination chemotherapy and 3 months after starting atezolizumab maintenance therapy...She received 2 cycles of irinotecan, given weekly as bridging therapy...After 1 day of lymphodepletion (fludarabine 30 mg/m 2 and cyclophosphamide 300 mg/m 2 ), she was excluded from the trial due to safety concerns from AMS (prior to LB2102 infusion)...The CAR-T cells expanded and persisted for more than 6 months. These findings warrant further research of DLL3-targeted autologous cell therapies for cancer."

CAR T-Cell Therapy • Clinical • IO biomarker • Anemia • CNS Disorders • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • CD4 • CRP • CTCs • DLL3 • TGFBR2

Phase 1 Study of DLL3-Targeted CAR-T Cells Armored With dnTGFBR2 in Small-Cell Lung and Large-Cell Neuroendocrine Cancers (IASLC-WCLC 2025) - "Methods : This 3+3 dose-escalation study assesses safety, dose-limiting toxicities (DLTs), and efficacy of LB2102 across 7 dose-levels (0.3-16.0×10E6 CAR+T cells/kg) following fludarabine and cyclophosphamide lymphodepletion. A dose-dependent efficacy signal was observed; higher dose levels were associated with increased response rates, CAR-T expansion, and response duration. Evaluation at higher dose levels is warranted to assess LB2102's therapeutic potential."

CAR T-Cell Therapy • IO biomarker • P1 data • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3 • TGFBR2

Safety, tolerability, and preliminary efficacy results of a phase 1 study of LB2102, a dnTGFβRII armored DLL3-targeted autologous CAR-T cell therapy, in patients with relapsed or refractory small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC). (ASCO 2025) - P1 | "All subjects undergo 3-day lymphodepletion (LD) with fludarabine (30 mg/m2), and cyclophosphamide (300 mg/m2)... LB2102 has been well tolerated with no DLT observed up to DL3 (2 x 106 CAR+ T cells/kg). There appears to be a dose-dependent efficacy signal observed at higher doses with responses correlating to CAR-T expansion, although the data is limited. Given no DLTs and preliminary efficacy signal up to DL3, further exploration of higher dose levels is warranted."

CAR T-Cell Therapy • Clinical • P1 data • Anemia • Endocrine Cancer • Large Cell Carcinoma • Leukopenia • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3 • TGFB1

LB2102 CAR T-Cell Therapy Is Well Tolerated, Yields Disease Control in R/R SCLC and LCNEC (OncLive) - P1 | N=41 | NCT05680922 | Sponsor: Legend Biotech USA Inc | "LB2102, a DLL3-directed autologous CAR T-cell therapy, was well tolerated without any dose-limiting toxicities (DLTs) observed up to dose level 4 (DL4), and it demonstrated preliminary antitumor activity in patients with relapsed/refractory small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), according to preliminary results from a phase 1 trial (NCT05680922) presented at the 2025 ASCO Annual Meeting. The best overall responses included partial responses (PRs) in 1 patient at dose level 3 (DL3) and 1 patient at DL4, and stable disease (SD) in 3 patients at dose level 2 (DL2), 2 patients at DL3, and 1 patient at DL4. In the overall population (n = 12), the objective response rate (ORR) was 16.7% with a disease control rate of 66.7%."

P1 data • Neuroendocrine Tumor • Small Cell Lung Cancer

Legend Biotech Announces New Oncologic & Hematologic Therapeutic Developments at ASCO, EHA, and ASGCT (Legend Biotech) - "Legend Biotech Corporation...announced...that new data evaluating CARVYKTI (ciltacabtagene autoleucel; cilta-cel) for patients living with multiple myeloma will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the 2025 European Hematology Association’s (EHA) Congress. Preliminary results from Phase 1 LB2102 and Phase 1 LB1908 ongoing dose-escalation studies in solid tumors, specifically lung and gastric cancers respectively, will also be featured in poster presentations at ASCO."

P1 data • P1/2 data • P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Multiple Myeloma • Small Cell Lung Cancer

dnTGF β RII-A rmored DLL3-Targeted CAR-T Cells Maintain TGF β Resistance with Early Signals of T-Cell Exhaustion Modulation After Expansion in SCLC (ASGCT 2025) - P1 | "LB2102 CAR VHHs demonstrated high specificity and no cross-reactivity to other DLL family members or unrelated proteins. LB2102 cells did not exhibit off-target killing in a panel of human primary cells (n=13). To assess whether dnTGFβRII expression confers resistance to TGFβ, LB2102 cells and unarmored LCAR-T20 cells were incubated with TGFβ1, and SMAD2 phosphorylation was assessed as a readout for TGFβ1-mediated signal transduction."

CAR T-Cell Therapy • IO biomarker • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3 • TGFB1 • TIGIT

First Quarter 2025 Financial Results (GlobeNewswire) - "License revenue was $9.3 million for the three months ended March 31, 2025, compared to $12.2 million for the three months ended March 31, 2024. The decrease of $2.9 million was solely attributed to revenue recognized pursuant to Legend Biotech’s license agreement with Novartis for the development, manufacture, and commercialization of LB2102 and other potential CAR-T therapies selectively targeting DLL-3 (the 'Novartis License Agreement'). This revenue is recognized over time as Legend Biotech conducts a Phase 1 clinical trial for LB2102. The decrease resulted from the timing of the underlying activities performed in connection with such trial....Selling and distribution expenses were $41.0 million for the three months ended March 31, 2025, compared to $24.2 million for the three months ended March 31, 2024. The increase was due to increased costs associated with commercial activities including expansion of the sales force due to growing sales of CARVYKTI."

Commercial • Multiple Myeloma • Solid Tumor

Legend Biotech Reports First Quarter 2024 Results and Recent Highlights (Businesswire) - "First Quarter 2024 Financial Results License Revenue...License revenue was $12.2 million for the first quarter of 2024 and consisted of the recognition of deferred revenue in connection with the global license agreement with Novartis Pharma AG to develop, manufacture, and commercialize LB2102 and other potential CAR-T therapies selectively targeting DLL3. Legend did not recognize any license revenue for the first quarter of 2023....Cost of License and Other Revenue: Cost of license and other revenue for the three months ended March 31, 2024 was $5.6 million and consisted of costs in connection with the global license agreement with Novartis Pharma AG to develop, manufacture, and commercialize LB2102 and other potential CAR-T therapies selectively targeting DLL3. The Company did not incur any cost of license and other revenue for the three months ended March 31, 2023."

Commercial • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Legend Biotech Announces Closing of License Transaction for Certain CAR-T Therapies Targeting DLL3 (Businesswire) - "Legend Biotech Corporation...closed its previously announced exclusive, worldwide license agreement with Novartis Pharma AG (Novartis) for certain Legend Biotech chimeric antigen receptor T-cell (CAR-T) cell therapies targeting Delta-like ligand protein 3 (DLL3), including Legend Biotech’s existing autologous CAR-T cell therapy candidate, LB2102 (NCT05680922). Under the terms of the license agreement closed today, Legend Biotech will receive a $100 million upfront cash payment."

Financing • Licensing / partnership • Solid Tumor

Phase 1 study of DLL3-directed chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer (SITC 2023) - P1 | "3 4 Preclinical studies of LB2102, an autologous DLL3-directed CAR-T cell, have demonstrated DLL3-specific antitumor effects with a low risk of on-target/off-tumor toxicities and off-target/off-tumor toxicities...Subjects may receive optional bridging therapy followed by lymphodepletion chemotherapy with fludarabine and cyclophosphamide for 3 days...The objectives of the study include characterization of safety and tolerability, evaluation of the recommended phase 2 dose, and assessment of preliminary antitumor activity. US sites will begin enrollment in fall 2023."

CAR T-Cell Therapy • Clinical • P1 data • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Legend Biotech Announces Exclusive, Global License Agreement for Certain CAR-T Therapies Targeting DLL3 (Businesswire) - "Legend Biotech Corporation...announced today that Legend Biotech Ireland Limited, a wholly owned subsidiary of Legend Biotech, has entered into an exclusive, global license agreement (License Agreement) with Novartis Pharma AG for certain Legend Biotech chimeric antigen receptor T-cell (CAR-T) cell therapies targeting DLL3, including its autologous CAR-T cell therapy candidate, LB2102 (NCT05680922). The License Agreement grants Novartis the exclusive worldwide rights to develop, manufacture and commercialize these cell therapies, and Novartis may apply its T-Charge™ platform to their manufacture...Under the License Agreement, Legend Biotech will conduct a Phase 1 clinical trial for LB2102 in the U.S. Novartis will conduct all other development for the licensed products....Under the terms of the License Agreement, Legend Biotech will receive a $100 million upfront payment and will be eligible to receive up to $1.01 billion in clinical, regulatory and commercial..."

Licensing / partnership • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=41 | Recruiting | Sponsor: Legend Biotech USA Inc | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Orphan Designation: Treatment of small cell lung cancer (FDA) - Date Designated: 06/21/2023

Orphan drug • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=41 | Not yet recruiting | Sponsor: Legend Biotech USA Inc

CAR T-Cell Therapy • New P1 trial • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Legend Biotech Announces FDA Clearance of IND Application for LB2102 in Extensive Stage Small Cell Lung Cancer (Businesswire) - "Legend Biotech Corporation...that the U.S. Food and Drug Administration (FDA) has cleared Legend Biotech’s Investigational New Drug (IND) application to proceed with the clinical development of LB2102, an investigational, autologous chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of adult patients with extensive stage small cell lung cancer (SCLC)....The Phase 1, first-in-human, open-label clinical study is designed to evaluate the safety and preliminary efficacy of LB2102 in subjects with extensive stage SCLC and patients with LCNEC, as well as to determine the recommended dose for Phase 2."

IND • New P1 trial • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer