Chinese Innovative Biotech Secures $1.1B Global Licensing Deal with Novartis for DLL3-Targeted CAR-T Therapy LB2102

On November 13, Legend Biotech announced that its wholly-owned subsidiary, Legend Biotech Ireland Limited, had entered into an exclusive global licensing agreement with Novartis for Legend Biotech’s specific DLL3-targeted chimeric antigen receptor T-cell (CAR-T) therapies, including its autologous CAR-T cell therapy candidate LB2102. The licensing agreement grants Novartis worldwide exclusive rights to develop, manufacture, and commercialize these cell therapies, allowing Novartis to apply its T-Charge platform in their production.

Following the FDA's approval of its new drug IND application in 2022, Legend Biotech is initiating clinical development of LB2102 for the treatment of extensive-stage small cell lung cancer and large cell neuroendocrine carcinoma. In 2023, the FDA granted the candidate product "Orphan Drug" designation.

According to the licensing agreement, Legend Biotech will conduct a Phase I clinical trial of LB2102 in the United States, and Novartis will be responsible for all other development of the licensed product.

According to the terms of the licensing agreement, Legend Biotech will receive an upfront payment of $100 million and is eligible for up to $1.01 billion in clinical, regulatory, and commercial milestone payments, as well as tiered royalties ($1.01 billion is approximately 7.363 billion RMB).

LB2102, developed by Legend Biotech, is a CAR-T therapy targeting Delta-Like Ligand 3 (DLL3). DLL3 is a potential target that is widely expressed in small cell lung cancer (SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), certain neuroendocrine cancers, and prostate cancer.

LB2102 utilizes VHH antibody technology and an "armed" CAR-T technology designed to overcome inhibitory factors in the tumor microenvironment. It carries two VHH antibody fragments that recognize DLL3, along with a transmembrane protein that can be activated by signals in the tumor microenvironment.

Preclinical studies show that this therapy can shrink tumors more effectively compared to traditional CAR-T therapy, with a significant increase in both the number of CAR-T cells in peripheral blood and those infiltrating the tumor.

As a CAR-T cell therapy for the treatment of solid tumors, the breakthrough of LB2102 represents that cell therapy produced in China has gained international recognition and achieved a phased victory in the field of solid tumors.

Small Cell Lung Cancer (SCLC) is an aggressive malignant tumor characterized by a high proliferation rate, propensity for metastasis, high recurrence, and poor prognosis. The survival rate of SCLC patients is very low, and there is an urgent need for new therapeutic targets and treatment approaches.

DLL3 Becomes a Rising Star Target in Small Cell Lung Cancer (SCLC) Treatment; LB2102 is Also Conducting SCLC-Related Clinical Trials. Currently, Various Types of DLL3-Targeted Drugs Are Under Research Globally, Including Monoclonal Antibodies, Multi-Antibodies, ADCs, and CAR-T. Legend Biotech and Amgen Are in the First Tier of DLL3 CAR-T Therapy Development.

Dr. Guowei Fang, Chief Scientific Officer and Head of Business Development at Legend Biotech, stated: "We believe that LB2102, with its innovative CAR design and armored mechanism, has the potential to enhance its anti-tumor activity. Preclinical evidence suggests that autologous CAR-T could be a differentiated treatment option for patients with small cell lung cancer. We are excited that a large pharmaceutical company with deep roots in oncology and cell therapy has chosen to advance this candidate into clinical trials. It is encouraging that the unique candidate design of LB2102, combined with the T-Charge platform, holds the potential to deliver transformative benefits to patients with small cell lung cancer."

Notably, in the disclosed transaction details, Novartis specifically emphasized its decision to incorporate the T-Charge platform into the manufacturing process of these therapies.

Novartis' T-Charge Platform is a next-generation CAR-T cell therapy production platform designed to maintain the stemness of T cells and promote the primary expansion of CAR-T cells in vivo. The T-Charge platform aims to reduce the need for prolonged ex vivo culturing, enabling T cells to have greater proliferation potential and reducing exhausted T cells.

Jennifer Brogdon, Ph.D., Head of Cell Therapy Research at the Exploratory Immuno-Oncology Department of the Novartis Institutes for BioMedical Research in 2022, once stated that biotech companies focusing on CAR-T have contacted Swiss pharmaceutical companies to explore the possibility of providing T-Charge therapy for their own drug candidates.

LB2102 will be Novartis' first application of T-Charge to a cell therapy candidate targeting solid tumors. LB2102 not only marks the first time Novartis has translated the capabilities of its T-Charge platform into an externally developed CAR-T, but also the first time it has been used in a cell therapy focused on solid tumors.

"We have previously explored CAR-T in solid tumors and believe that our T-Charge platform, combined with Legend Biotech's unique CAR design, will provide patients with more potent and durable innovative therapies," Brogdon said.

In 2017, the world's first CAR-T therapy was approved by the FDA for marketing, developed by Novartis in collaboration with the University of Pennsylvania. In the same year, Legend Biotech signed a collaborative development agreement for its BCMA CAR-T with Janssen, with an upfront payment as high as $350 million. In 2023, Legend Biotech’s DLL3 CAR-T once again completed a significant License-out agreement, with the collaborator being none other than Novartis, the global pioneer in CAR-T therapy.

Not only that, but Legend Biotech and Novartis had already laid the groundwork for their collaboration.

Previously, through its collaboration with Janssen, Legend Biotech’s first product, CARVYKTI (ciltacabtagene autoleucel, cilta-cel), was approved for marketing by the U.S. FDA and Japan's Ministry of Health, Labour and Welfare (MHLW) in 2022. It also received conditional marketing authorization from the European Commission (EC), showing potential to address a worldwide challenge in the treatment of multiple myeloma. By the end of 2022, China's National Medical Products Administration (NMPA) officially accepted the New Drug Application (NDA) for ciltacabtagene autoleucel, and it was included in the priority review process in January 2023. Additionally, the company has several cell therapies under development for the treatment of hematological malignancies, solid tumors, and other complex diseases.

In April this year, Legend Biotech/Johnson & Johnson and Novartis signed a CMO contract, under which Novartis will provide Carvykti production services for the former for three years to address capacity shortages.

For Legend Biotech, this is another major BD deal following the collaboration with Johnson & Johnson on Carvykti, encompassing both hematologic CAR-T and solid tumor CAR-T, making it the leading "CAR-T player" in China.

As the R&D boom and iteration speed of the cell track in China continue to accelerate, we seem to foresee that the next goal of cell therapy will be to address the clinical needs of solid tumors and improve accessibility. In the future, we also look forward to seeing more innovative cell therapies emerge.