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.

About PackGene

PackGene is a CRO & CDMO technology company that specializes in packaging recombinant adeno-associated virus (rAAV) vectors. Since its establishment in 2014, PackGene has been a leader in the AAV vector CRO service field, providing tens of thousands of custom batches of AAV samples to customers in over 20 countries. PackGene offers a one-stop CMC solution for the early development, pre-clinical development, clinical trials, and drug approval of rAAV vector drugs for cell and gene therapy (CGT) companies that is fast, cost-effective, high-quality, and scalable. Additionally, the company provides compliant services for the GMP-scale production of AAVs and plasmids for pharmaceutical companies, utilizing five technology platforms, including the π-Alpha 293 cell AAV high-yield platform and the π-Omega plasmid high-yield platform. PackGene's mission is to make gene therapy affordable and accelerate the launch of innovative gene drugs. The company aims to simplify the challenging aspects of gene therapy development and industrialization processes and provide stable, efficient, and economical rAAV Fast Services to accelerate gene and cell therapy development efforts from discovery phase to commercialization.

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