Single-Cell Multi-Omics Analysis of IASO Bio's Equecabtagene Autoleucel in the Treatment of Autoimmune Diseases of the Central Nervous System Published in Science Immunology

SHANGHAI, NANJING, China, and SAN JOSE, Calif., May 11, 2024 /PRNewswire/ -- On May 10, 2024, the impactful international academic journal, Science Immunology, a sub-journal of Science, published a research paper titled "Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity". This paper focuses on the single-cell multi-omics analysis of the fully human BCMA targeting autologous CAR-T cell injection (Equecabtagene Autoleucel, Eque-cel, R&D code: CT103A) in the treatment of patients with neuromyelitis optica spectrum disorder (NMOSD). This paper described for the first time in the world the dynamic evolutionary trajectories of CAR-T cells in patients with autoimmune diseases, analyzed the molecular characteristics of central infiltration of CAR-T cells, revealed the mechanism of immune remodeling in the central nervous system during CAR-T therapy for autoimmune diseases of the central nervous system, and elucidated the molecular differences of CAR-T cells between patients with autoimmune diseases and cancers at the cellular and molecular levels.

In 2022, IASO Bio published the interim results of an investigator-initiated phase I clinical study of Eque-cel in the treatment of neuromyelitis optica spectrum disorder (NMOSD) on the Signal Transduction and Targeted Therapy (IF = 38.1), the sub-journal of Nature, which preliminarily demonstrated the good tolerability and safety, durable pathogenic antibody clearance, and potential clinical efficacy of Eque-cel in NMOSD. However, the cell kinetics and immunological characteristics of CAR-T cells in the treatment of autoimmune diseases of the central nervous system are still unclear.

This is an investigator-initiated open-label study to evaluate the safety and efficacy of Eque-cel for the treatment of relapsed/refractory antibody-mediated idiopathic inflammatory disorders of the nervous system (NCT04561557).  It was conducted by Prof. Wei Wang's team at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

In this study, single-cell multi-omics analysis was performed on blood and cerebrospinal fluid (CSF) samples from 5 patients with relapsed or refractory AQP4-positive NMOSD and 5 patients with multiple myeloma treated with Eque-cel to study the in vivo characteristics of CAR-T cells in patients with autoimmune diseases. The study found that there was only a 13% overlap in the B cell immunoglobulin heavy chain variable region (IgVH) sequences between the peripheral blood and CSF of patients with NMOSD, suggesting that B cells in the CSF are mostly derived from B cells intrinsic to the central nervous system rather than from the peripheral blood. CAR-T cells with chemotactic properties can cross the blood-brain barrier and enter the central nervous system to directly kill abnormal plasma cells in the central nervous system. The action facilitates the restoration of central immunity as it reduces the secretion of autoantibodies within sheaths and the abnormal activation of immune cells. As a result, the immune disorder in the central nervous system of the NMOSD patients can be rectified and its immune system can be reset. The study shows that CAR-T cells predominantly exhibit a CD8⁺ cycling CAR-T cell phenotype in patients with immune diseases, and the cytotoxic function of CAR-T cells is reduced compared with the control group. The above characteristics explain the relatively low grade of CRS and relatively short survival time of CAR-T cells in patients with immune diseases after CAR-T therapy, which is conducive to earlier immune remodeling in patients, and further confirms the good safety of Eque-cel in autoimmune diseases.

Professor Wei Wang from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the principal investigator of this study, said " With the continuous emergence of innovative clinical studies of CAR-T cells in the treatment of autoimmune diseases in different countries and regions around the world, experts around the world have attached increasing importance to and recognized the prospects of such innovative cell therapy for patients with relapsed and refractory immune diseases. This study is the first in-depth single-cell multi-omics analysis of multiple types of body fluids from NMOSD patients in the world, depicting the dynamic evolutionary trajectories of CAR-T cells in patients with immune diseases at the cellular and molecular level. In particular, we found that CAR-T cells with chemotactic properties can more easily cross the blood-brain barrier and enter the central nervous system to directly kill abnormal immune cells in the central nervous system. This discovery is very critical for the treatment of immune abnormalities in the central nervous system. We also noted different characteristics in CAR-T cells between autoimmune patients and tumor patients, which provided scientific insights into refining CAR-T cell therapies for autoimmune diseases."

Ms. Jinhua Zhang, the Founder and Chief Executive Officer of IASO Bio, said, "I am very pleased that another research achievement of Eque-cel for the treatment of autoimmune diseases has been published in Science Immunology. This is the third academic article in the field of autoimmunity published in internationally impactful journals through the collaboration between IASO Bio and the team led by Professor Wei Wang at Tongji Hospital in Wuhan this year. This research achievement has once again created a "world first", further validating the efficacy, safety and persistence of CAR-T therapy in the treatment of autoimmune diseases, and once again firming the determination of IASO Bio to continue to focus on the development of CAR-T products in the field of autoimmunity. Currently, IASO Bio has obtained INDs for multiple autoimmune diseases, including NMOSD and MG, in both China and the United States, and plans to accelerate the progress of these projects. In terms of BD collaboration in the field of autoimmunity, we entered into a licensing agreement with Cabaletta Bio, a US cell therapy company, in 2022. We granted Cabaletta exclusive rights globally to develop, produce, and commercialize CAR-T therapies for autoimmune diseases using our clinically validated, fully human CD19 binder. Currently, the product has received IND approvals for a number of autoimmune indications, including systemic lupus erythematosus (SLE) / lupus nephritis (LN), idiopathic inflammatory myopathies (IIM), systemic sclerosis（SSc）and generalized myasthenia gravis（gMG）, and is steadily progressing through clinical trials. We are actively seeking to expand our global BD collaborations in the autoimmune area to accelerate product development so that  autoimmune patients worldwide would be able to use  safer and more effective treatments at an early date."

About IASO Bio

IASO Bio is a biopharmaceutical company engaged in the discovery and development of novel cell therapies and biologics for oncology and autoimmune diseases. IASO Bio possesses comprehensive capabilities spanning the entire drug development process, from early discovery to clinical development, regulatory approval, and commercial production.

The pipeline in the company includes a diversified portfolio of over 10 novel products, including Equecabtagene Autoleucel (a fully human BCMA CAR-T injection). Equecabtagene Autoleucel received New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S. FDA IND approval for the treatment of RRMM.

Leveraging its strong management team, innovative product pipeline, GMP production, as well as integrated manufactural and clinical capabilities, IASO aims to deliver transformative and curable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit http://www.iasobio.com or www.linkedin.com/company/iasobiotherapeutics.