PHE-885

LB2102 will mark the first time Novartis has turned the power of its T-Charge platform to a solid-tumor-focused cell therapy. Novartis will give a solid-tumor-focused cell therapy the T-Charge treatment, after paying $100 million upfront to Legend Biosciences 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.

Novartis has struck a licensing deal to advance some of Legend Biotech's experimental CAR T-cell therapies targeting DLL3, including its autologous CAR-T candidate LB2102. As part of the deal announced Monday, Novartis will pay Legend $100 million upfront, and has committed to additional milestone payments of up to $1.01 billion upon the achievement of certain clinical, regulatory and commercial targets.A first-in-human Phase I study of LB2102 began in July for the treatment of extensive-stage small-cell lung cancer (SCLC) or large-cell neuroendocrine carcinoma. "We believe LB2102 has an innovative CAR design and armour mechanism that increases its anti-tumour activity," commented Legend's chief scientific officer Guowei Fang, highlighting preclinical evidence that suggests an autologous CAR-T could offer up a differentiated approach for SCLC patients. The Phase I trial of LB2102 has an estimated enrollment of 41 participants and is expected to read out in 2028.Better proliferative potentialThe new licensing deal grants Novartis exclusive worldwide rights to Legend's DLL3-targeting CAR-T therapies, and allows the Swiss drugmaker to apply its T-Charge platform to their manufacture. The platform is designed to preserve T-cell stemness, or the ability to self-renew and mature, resulting in a product that contains greater proliferative potential and fewer exhausted T-cells. With this technology, the expansion of CAR T-cells occurs primarily in vivo, thus eliminating the need for an extended culture time outside of the body, Novartis says. LB2102 would be the first application of T-Charge by Novartis to a cell therapy candidate targeting solid tumours.Under the agreement, Legend will conduct the Phase I trial for LB2102 in the US, while Novartis takes on all other development for licensed products. Aside from the upfront and potential milestone payments, Legend would also be eligible for tiered royalties on any commercialised products down the road.Novartis is currently developing the CD19-directed CAR-T rapcabtagene autoleucel, also known as YTB323, for lupus nephritis and first-line high-risk large B-cell lymphoma in Phase II, as well as for adult acute lymphoblastic leukaemia in a Phase I trial. The company is also working on PHE885, another T-Charge manufactured CAR-T cell therapy, this time directed against BCMA for patients with relapse/refractory multiple myeloma.