Novartis pays Legend $100M upfront to give solid tumor CAR-T the T-Charge treatment

Novartis will give a solid-tumor-focused cell therapy the T-Charge treatment, after paying $100 million upfront to Legend Biotech for a selection of CAR-T candidates.

The therapies in question all target Delta-like ligand protein 3 (DLL3), including an autologous CAR-T dubbed LB2102 that Legend has taken into the clinic for lung cancer. What makes this deal especially noteworthy is Novartis’ decision to incorporate its T-Charge platform in the manufacturing process of these therapies.

The T-Charge process involves a significant portion of CAR T-cell expansion taking place within the patient’s body. By minimizing the time the cells spend outside the body (ex vivo), it aims to preserve naive and stem cell memory T cells. According to the theory, this preservation may result in better responses, improved long-term outcomes and a reduced risk of severe adverse events.

Last year, Jennifer Brogdon, Ph.D., head of cell therapy research in the Department of Exploratory Immuno-Oncology of the Novartis Institutes for BioMedical Research, told Fierce Biotech that CAR-T-focused biotechs had already been in contact with the Swiss pharma to explore the possibility of giving their own candidates the T-Charge treatment.

LB2102 will mark not only the first time Novartis has turned the power of its T-Charge platform onto an externally-developed CAR-T but also the first time it has been used on a solid-tumor-focused cell therapy, the Big Pharma said. Legend will oversee a phase 1 trial of LB2102 in the U.S., before Novartis takes over all further development.

“We have explored CAR-T in solid tumors previously and believe that our T-Charge platform coupled with Legend Biotech’s unique CAR design may add a level of potency and persistence needed to provide transformative benefit for patients,” Brogdon told Fierce Biotech via email this morning.

Beyond the hefty $100 million upfront payment, the New Jersey-based biotech is also in line for over $1 billion in potential milestone payments as well as tiered royalties.

“We believe LB2102 has an innovative CAR design and armor mechanism that increases its anti-tumor activity,” Legend’s chief scientific officer Guowei Fang, Ph.D., said in the release. “We are excited that a major pharmaceutical company with deep roots in oncology and cell therapy has chosen to further this product candidate in the clinic.”

Novartis already has two homegrown CAR-T therapies in the clinic that were produced by the T-Charge platform. Rapcabtagene autoleucel, also known as YTB323, has been shown to produce a 63% complete response rate after three months among 26 patients with relapsed/refractory diffuse large B-cell lymphoma in a phase 1 trial. The other asset, PHE885, has demonstrated a 96% overall response rate among the 23 patients with relapsed/refractory multiple myeloma.

Since then, Novartis has remained loyal to the platform’s potential. T-Charge can only be used for autologous therapies, and Novartis has so far resisted the hype around so-called “off-the-shelf” CAR-Ts.

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