Focused on rapidly developing cell therapies
Our global R&D network allows us to increase speed of clinical development
Legend Biotech remains fearless in our research
To accelerate the science and bring innovative therapies to patients, we will:
Program areas of development
Legend Biotech is utilizing the extensive cell therapy experience of our leadership and R&D staff, global clinical partners, and expanding research facilities to realize the potential of cell therapy to treat diseases that are thought to be incurable, such as hematologic malignancies, solid tumors, infectious diseases, and autoimmune diseases.
We are rapidly advancing our 3 core cell therapy platforms:
LCAR-B38M/JNJ-4528*
Our first product candidate, LCAR-B38M/JNJ-4528, is a B cell maturation antigen (BCMA)-directed CAR-T cell therapy. BCMA is highly expressed on myeloma cells and plasma cells.1,2 Proof of concept has been achieved in an investigator-initiated, first-in-human study (LEGEND-2) conducted in 74 patients with RRMM in China.1,3 Globally, Legend Biotech, together with Janssen Biotech, Inc., is advancing the Phase 1b/2 trial (CARTITUDE-1, NCT03548207) with JNJ-4528 to evaluate its efficacy and safety in adults with RRMM. The study is currently enrolling patients following US Food and Drug Administration clearance of an Investigational New Drug application as announced in May 2018.
A Phase 2 confirmatory trial (CARTIFAN-1, CTR20181007, NCT03758417) registered with the Center for Drug Evaluation is currently enrolling patients in China to further evaluate LCAR-B38M in patients with advanced RRMM.
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Binding Domains
Other CARs typically have a single binding domain. However, LCAR-B38M/JNJ-4528 CAR-T cells contain 2 single-domain antibodies that target BCMA.
Spacer/hinge and transmembrane domains
Influences the length and flexibility of the CAR, which may affect tumor recognition, CAR expression, and T-cell activation.4
Costimulatory domain (4-1BB)
Transmits costimulatory signals for T-cell proliferation and enhanced persistence of LCAR-B38M/JNJ-4528.
T-cell activation domain (CD3ζ)
Provides the primary signal for T-cell activation.
LCAR-B38M/JNJ-4528 — a structurally differentiated CAR-T cell therapy containing a 4-1BB co-stimulatory domain and two BCMA-targeting single-domain antibodies designed to confer avidity
RRMM=relapsed or refractory multiple myeloma
TCR-T
Legend Biotech recognizes that T-cell receptors (TCRs) isolated from tumor-specific T cells can be another effective approach to target tumors; in particular, solid tumors. Unlike CARs, TCRs can bind to polypeptides (antigens) derived from intracellular proteins.
Mutations with altered protein sequences occur frequently in many cancers. The mutated proteins are cleaved inside the cell and presented on the cell surface as polypeptides (epitopes) by the major histocompatibility complex (MHC). Neoepitopes are polypeptides derived from mutated genes/proteins presented only on tumors but not normal cells, which can be highly immunogenic and induce potent anti-tumor T-cell responses. TCRs isolated from neoepitope-specific T cells can then be engineered to TCR-T for clinical use.
At Legend Biotech, we are addressing the challenges of treating solid tumors by identifying novel TCRs to build TCR-T based on a foundation of studying with the leaders in the field, and further improving TCR-T as therapeutics by overcoming the immunosuppressive tumor microenvironment.
Allogeneic
Legend Biotech sees the promise of allogeneic cell therapy and its potential benefits. We are exploring a range of versatile tools and cell types in pursuit of a truly “off-the-shelf” cell therapy.
LCAR-B38M/JNJ-4528*
Our first product candidate, LCAR-B38M/JNJ-4528, is a B cell maturation antigen (BCMA)-directed CAR-T cell therapy. BCMA is highly expressed on myeloma cells and plasma cells.1,2 Proof of concept has been achieved in an investigator-initiated, first-in-human study (LEGEND-2) conducted in 74 patients with RRMM in China.1,3 Globally, Legend Biotech, together with Janssen Biotech, Inc., is advancing the Phase 1b/2 trial (CARTITUDE-1, NCT03548207) with JNJ-4528 to evaluate its efficacy and safety in adults with RRMM. The study is currently enrolling patients following US Food and Drug Administration clearance of an Investigational New Drug application as announced in May 2018.
A Phase 2 confirmatory trial (CARTIFAN-1, CTR20181007, NCT03758417) registered with the Center for Drug Evaluation is currently enrolling patients in China to further evaluate LCAR-B38M in patients with advanced RRMM.
Binding Domains
Other CARs typically have a single binding domain. However, LCAR-B38M/JNJ-4528 CAR-T cells contain 2 single-domain antibodies that target BCMA.
Spacer/hinge and transmembrane domains
Influences the length and flexibility of the CAR, which may affect tumor recognition, CAR expression, and T-cell activation.4
Costimulatory domain (4-1BB)
Transmits costimulatory signals for T-cell proliferation and enhanced persistence of LCAR-B38M/JNJ-4528.
T-cell activation domain (CD3ζ)
Provides the primary signal for T-cell activation.
LCAR-B38M/JNJ-4528 — a structurally differentiated CAR-T cell therapy containing a 4-1BB co-stimulatory domain and two BCMA-targeting single-domain antibodies designed to confer avidity
RRMM=relapsed or refractory multiple myeloma
TCR-T
Legend Biotech recognizes that T-cell receptors (TCRs) isolated from tumor-specific T cells can be another effective approach to target tumors; in particular, solid tumors. Unlike CARs, TCRs can bind to polypeptides (antigens) derived from intracellular proteins.
Mutations with altered protein sequences occur frequently in many cancers. The mutated proteins are cleaved inside the cell and presented on the cell surface as polypeptides (epitopes) by the major histocompatibility complex (MHC). Neoepitopes are polypeptides derived from mutated genes/proteins presented only on tumors but not normal cells, which can be highly immunogenic and induce potent anti-tumor T-cell responses. TCRs isolated from neoepitope-specific T cells can then be engineered to TCR-T for clinical use.
At Legend Biotech, we are addressing the challenges of treating solid tumors by identifying novel TCRs to build TCR-T based on a foundation of studying with the leaders in the field, and further improving TCR-T as therapeutics by overcoming the immunosuppressive tumor microenvironment.
Allogeneic
Legend Biotech sees the promise of allogeneic cell therapy and its potential benefits. We are exploring a range of versatile tools and cell types in pursuit of a truly “off-the-shelf” cell therapy.
References: 1. Zhao WH, Liu J, Wang BY, et al. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018;11(1):141. 2. Carpenter RO, Evbuomwan MO, Pittaluga S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19(8):2048-2060. 3. Xu J, Chen LJ, Yang SS, et al. Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Proc Natl Acad Sci USA. 2019;doi: 10.1073/pnas.1819745116. 4. Guedan S, Calderon H, Posey AD Jr, Maus MV. Engineering and design of chimeric antigen receptors. Mol Ther Methods Clin Dev. 2018;12:145-156. 5. Efremova M, Finotello F, Rieder D, Trajanoski Z. Neoantigens generated by individual mutations and their role in cancer immunity and immunotherapy. Front Immunol. 2017;8:1679. 6. Data on file. Piscataway, NJ: Legend Biotech USA Inc.
The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.
*LCAR-B38M identifies the investigational product being studied in China and Janssen Biotech, Inc.’s JNJ-68284528 (also referenced as JNJ-4528) identifies the investigational product being studied in the United States, both of which are representative of the same CAR-T cell therapy.
Rapid progress
Our milestones show our acceleration in product and infrastructure development
TIMELINE
2021
May: Created data from the Phase 1b portion of CARTITUDE-1 Presented at ASCO
May: Legend Biotech Reports New and Updated Data from BCMA CAR-T Program at 2021 ASCO and EHA Meetings
2020
May: Updated data from the Phase 1b portion of CARTITUDE-1 Presented at ASCO
May: Announced Collaborative Research and Licensing Agreement with Noile-Immune Biotech
2019
December: Initial result from the Phase 1b portion of CARTITUDE-1 presented at ASH 2019
December: JNJ-4528 granted Breakthrough Therapy Designation
May: Additional data from LEGEND-2 published in the Proceedings of the National Academy of Sciences of the United States of America
April: JNJ-4528 was granted the PRIME designation in the treatment of relapsed or refractory multiple myeloma
February: Joined other corporate industry leaders in the ASTCT Corporate Council
2018
December: Data from LEGEND-2 published in the Journal of Hematology & Oncology
December: Updated data from Phase 1/2 open-label study of LCAR-B38M (LEGEND-2) presented at ASH 2018
May: Phase 1b/2 IND for JNJ-4528 cleared by the FDA
March: Phase 2 IND for LCAR-B38M cleared by NMPA
2017
December: Worldwide collaboration and licensing agreement with Janssen signed in December
June: Results from an ongoing, early-phase clinical trial with LCAR-B38M presented at ASCO
2016
March: First RRMM patient treated with LCAR-B38M in China
2014
Legend Biotech business entity created
RRMM=relapsed or refractory multiple myeloma
The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.
*LCAR-B38M identifies the investigational product being studied in China and Janssen Biotech, Inc.’s JNJ-68284528 (also referenced as JNJ-4528) identifies the investigational product being studied in the United States, both of which are representative of the same CAR-T cell therapy.
