AstraZeneca's In Vivo CAR-T Therapy ESO-T01 Shows Promising Phase I Results Shortly After $1B Acquisition of EsoBiotec

Jul 13, 2025 07:00 CST Updated 07:00

AstraZeneca

Biopharmaceutical Manufacturer

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Just one month after AstraZeneca acquired Belgian biotech company EsoBiotec for up to $1 billion, on July 7, the first set of clinical data for its core asset, the investigational in vivo CAR-T therapy ESO-T01, was disclosed in The Lancet, providing a strong boost to this traditional pharmaceutical company's cell and gene therapy strategy.

This Phase I trial, conducted on four Chinese patients with refractory multiple myeloma, demonstrated that ESO-T01 exhibited positive efficacy shortly after a single intravenous infusion: two patients achieved stringent complete response (sCR), and two attained partial response (PR). Notably, all subjects were extreme cases who had failed multiple lines of treatment — including penta-drug resistance with extensive extramedullary metastasis, relapse post-stem cell transplantation, resistance to fourth-line therapy with large-scale extramedullary lesions, and failure of prior BCMA-targeted CAR-T therapy.

Unlike the complex process of traditional CAR-T therapy, which requires the extraction, modification, and reinfusion of T cells outside the body, ESO-T01 adopts an innovative "in vivo programming" strategy: using a nanobody-targeted lentiviral vector to directly reprogram T cells into CAR-T cells within the patient’s body. This design aims to avoid the pain points of traditional therapies, such as "long manufacturing cycles, high costs, and long patient waiting times." The research team speculates that the smaller size of the viral particles may enhance tumor tissue penetration, while CAR-T cells generated in vivo may possess better tumor homing ability and adaptability to the tumor microenvironment.

In terms of specific efficacy, the first case of a patient with quintuple drug resistance achieved complete regression of bone marrow and extramedullary lesions in the second month of treatment; the second patient reached complete remission within 28 days; the latter two patients with partial remission showed reduction in tumor burden and conversion to negative minimal residual disease in the bone marrow. In terms of safety, all patients only experienced Grade 1 cytokine release syndrome (CRS), and one patient with high tumor burden developed Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS), both effectively controlled with glucocorticoids. Hematological toxicity mainly manifested as Grade 3-4 neutropenia, which resolved in most cases during the follow-up period; two patients developed pulmonary infections and recovered after antibiotic treatment.

This acquisition is a key step for AstraZeneca to deepen its layout in cell and gene therapy. The company secured the rights to ESO-T01 with a $425 million upfront payment and $575 million in milestone payments, continuing its recent series of moves in this field, having already built a technological moat by investing in companies such as Gracell and Neogene Therapeutics. With the release of the first clinical data, the subsequent development progress of this disruptive in vivo CAR-T therapy will become an important benchmark for evaluating the effectiveness of traditional pharmaceutical companies transitioning into innovative biotechnology.

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