So far, Novartis has one in-house therapy in the clinic that was developed through the T-Charge process. Rapcabtagene autoleucel, also known as rap-cel or YTB323, a\u00a0CD19-targeted autologous CAR-T, is in phase 2 studies for blood cancers such as B-cell lymphoma, as well as for autoimmune indications such as lupus nephritis and systemic sclerosis.<\/p>\n
But while rap-cel has been working its way through the clinic, in vivo options\u2014which use gene editing to generate CAR-T cells within a patient\u2019s body\u2014have become the hottest play in town. Eli Lilly<\/a> has bought two in vivo biotechs this year alone, joining similar acquisitions by Gilead Sciences<\/a>, AbbVie<\/a>, Bristol Myers Squibb<\/a> and AstraZeneca<\/a>.<\/p>\n So has T-Charge already been overtaken before it\u2019s even brought a CAR-T to market? Novartis\u2019 cancer chiefs aren\u2019t so sure.<\/p>\n \u201cThe in vivo data that we’ve seen so far publicly\u2014it’s encouraging, but I think it’s early, right?\u201d Novartis\u2019 Global Head of Oncology Development, Mark Rutstein, M.D., told Fierce in an interview.<\/p>\n \u201cWe see early efficacy that’s promising,\u201d Rutstein continued. \u201cWe’ll have to see durability, because one of the hallmarks of \u2026 this T-Charge platform is durable efficacy, and so I think we just need to see more data in that regard.\u201d<\/p>\n While acknowledging that in vivo options have \u201ca lot of potential,\u201d Rutstein added that he believes \u201cthere’s opportunity for both platforms.\u201d<\/p>\n Another recent development in the CAR-T space has been applying this modality to autoimmune disease. Here, Novartis has remained toward the front of the pack. Rap-cel is in phase 2 development for the likes of lupus nephritis, systemic lupus erythematosus, systemic sclerosis and myositis. In fact, the company is aiming to submit the therapy to\u00a0regulators for lupus nephritis<\/a>\u00a0in 2028.<\/p>\n Despite rap-cel\u2019s origins lying in its potential as a lymphoma treatment, the current timeline for the CAR-T therapy in oncology is slightly less clear. Following the interim phase 2 data<\/a> published earlier this year, Rutstein was only able to say Novartis is \u201cactively discussing next steps\u201d for how to further explore rap-cel to treat cancers.<\/p>\n The two lymphoma studies for rap-cel have so far shown \u201cacceptable safety and competitive efficacy,\u201d said Rutstein. But he was keen to stress that CAR-Ts have potential \u201cbeyond the typical hematology setting,\u201d with Rutstein\u2019s neuroscience colleagues also interested in what cell therapies could offer.<\/p>\n <\/a><\/p>\n Shiva Malek<\/p>\n Shiva Malek, Ph.D., global head of oncology at Novartis Institutes for BioMedical Research At one point, Novartis had been evaluating a second T-Charge candidate, dubbed PHE885, in a phase 1 study for multiple myeloma. But despite execs telling Fierce<\/a> back in 2022 that the initial clinical data looked \u201creally promising,\u201d\u00a0Rutstein confirmed that the BCMA-based CAR-T has since been discontinued.<\/p>\n It means that beyond rap-cel, the biggest development in the T-Charge world has come from a hook-up with Legend Biotech. Novartis paid the biotech $100 million<\/a> back in 2023 for a selection of CAR-Ts.<\/p>\n The therapies all target delta-like ligand protein 3 (DLL3), and include an autologous CAR-T dubbed LB2102 that Legend had already\u00a0taken into the clinic<\/a>\u00a0for lung cancer. The idea was always for Novartis to incorporate T-Charge into the manufacturing process of these therapies, and the pharma is finally ready to put this plan into practice.<\/p>\n \u201cIt\u2019s still very early days on that,\u201d Shiva Malek, Ph.D., global head of oncology at Novartis Institutes for BioMedical Research, told Fierce in the same interview. \u201cWe are just getting ready to start the clinical studies for that program, but I think in general it\u2019s pretty exciting.\u201d<\/p>\n Malek namechecked the approval in 2024 of Amgen\u2019s<\/a> bispecific T-cell engager Imdelltra\u2014which targets both DLL3 and CD3\u2014as evidence that \u201cT-cell-targeting approaches should really have benefit in this context.\u201d<\/p>\n The continuing work on T-Charge doesn\u2019t mean that Novartis has no in-vivo strategy, however. The pharma signed a pact in 2024<\/a> to use Vyriad\u2019s active targeting lentiviral vector platform to discover and develop new in vivo CAR-T cell therapies.<\/p>\n
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\n (Novartis NIBR)<\/p>\n