Shanghai Tongji Hospital

SHANGHAI, NANJING, China, and SAN JOSE, Calif., May 10, 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 or . SOURCE IASO Bio

Atrial fibrillation is the most common cardiac arrhythmia worldwide with around 59 million people concerned in 2019. This irregular heartbeat is associated with increased risks of heart failure, dementia and stroke. It constitutes a significant burden to healthcare systems, making its early detection and treatment a major goal. Researchers have recently developed a deep-learning model capable of predicting the transition from a normal cardiac rhythm to atrial fibrillation. It gives early warnings on average 30 minutes before onset, with an accuracy of around 80%. These results pave the way for integration into wearable technologies, allowing early interventions and better patient outcomes. Atrial fibrillation is the most common cardiac arrhythmia worldwide with around 59 million people concerned in 2019. This irregular heartbeat is associated with increased risks of heart failure, dementia and stroke. It constitutes a significant burden to healthcare systems, making its early detection and treatment a major goal. Researchers from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have recently developed a deep-learning model capable of predicting the transition from a normal cardiac rhythm to atrial fibrillation. It gives early warnings on average 30 minutes before onset, with an accuracy of around 80%. These results, published in the scientific journal Patterns, pave the way for integration into wearable technologies, allowing early interventions and better patient outcomes. During atrial fibrillation, the heart's upper chambers beat irregularly and are out of sync with the ventricles. Reverting to a regular rhythm can require intensive interventions, from shocking the heart back to normal sinus rhythm to the removal of a specific area responsible for faulty signals. Being able to predict an episode of atrial fibrillation early enough would allow patients to take preventive measures to keep their cardiac rhythm stable. However, current methods based on the analysis of heart rate and electrocardiogram (ECG) data are only able to detect atrial fibrillation right before its onset and do not provide an early warning. "In contrast, our work departs from this approach to a more prospective prediction model," explains Prof. Jorge Goncalves, head of the Systems Control group at the LCSB. "We used heart rate data to train a deep learning model that can recognise different phases -- sinus rhythm, pre-atrial fibrillation and atrial fibrillation -- and calculate a "probability of danger" that the patient will have an imminent episode." When approaching atrial fibrillation, the probability increases until it crosses a specific threshold, providing an early warning. This artificial intelligence model, called WARN (Warning of Atrial fibRillatioN), was trained and tested on 24h-recordings collected from 350 patients at Tongji Hospital (Wuhan, China) and gave early warnings, on average 30 minutes before the start of atrial fibrillation, with great accuracy. Compared to previous work on arrhythmia prediction, WARN is the first method to provide a warning far from onset. "Another interesting aspect is that our model has a high performance using only R-to-R intervals, basically just heart rate data, that can be acquired from easy-to-wear and affordable pulse signal recorders such as smartwatches," highlights Dr Marino Gavidia, first author of the publication, who worked on this project during his PhD within the Systems Control group and the Doctoral Training Unit CriTiCS (see box below). "These devices can be used by patients on a daily basis, so our results open possibilities for the development of real-time monitoring and early warnings from comfortable wearable devices," adds Dr Arthur Montanari, a LCSB researcher involved in the project. Additionally, the deep-learning model developed by the researchers could be implemented in smartphones to process the data from a smartwatch. This low computational cost makes it ideal for integration into wearable technologies. The long-term objective is for patients to be able to continuously monitor their cardiac rhythm and receive early warnings that can provide sufficient time to take antiarrhythmic medication or use some targeted treatments to prevent the onset of atrial fibrillation. This in turn would reduce emergency interventions and improve patient outcomes. "Moving forward, we will focus on developing personalised models. The daily use of a simple smartwatch constantly provides new information on personal heart dynamics, enabling us to continuously refine and retrain our model for that patient to achieve enhanced performance with even earlier warnings," concludes Prof. Goncalves. "Eventually, this approach could even lead to new clinical trials and innovative therapeutic interventions."

SHANGHAI and NANJING, China and SAN JOSE, Calif., Feb. 29, 2024 /PRNewswire/ -- On February 26, 2024, the impactful international academic journal, EMBO Molecular Medicine, published the clinical data of the fully human BCMA targeting autologous CAR-T cell injection (Equecabtagene Autoleucel, Eque-cel, CT103A) for the treatment of two refractory myasthenia gravis (MG) subjects. B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis, initially demonstrated the good tolerability and safety of Eque-cel in the treatment of MG, as well as the durable clinical efficacy. MG is an autoimmune disease with acquired neuromuscular junction (NMJ) transmission disorders mediated by antibodies. Antibodies to the Acetylcholine Receptor (AChR) are the most common pathogenic antibodies; in addition, antibodies such as Muscle-Specific receptor tyrosine Kinase (MuSK), low-density Lipoprotein Receptor-related Protein 4 (LRP4), and Ryanodine Receptor (RyR), have also been found to be involved in the pathogenesis of MG. Currently, the treatment of MG is still based on cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulin, plasma exchange, and thymectomy. The main causes of death in MG patients include respiratory failure and pulmonary infections. 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. Two subjects with refractory MG were enrolled in this study. One was a 33-year-old female, AChR-IgG and Titin-IgG positive, who had been treated with thymectomy 21 months prior to enrollment and had not achieved clinical remission after treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and anti-CD20 monoclonal antibody. The other subject was a 60-year-old female, MuSK- IgG4 positive, with a 20-year history of the disease and failed the previous treatment with hormones, immunosuppressants, and anti-CD20 monoclonal antibody. The 2 subjects were treated with a single infusion of Eque-cel at the doses of 1.01×106 CAR-T/Kg and 0.96×106 CAR-T/Kg， respectively. Safety: Of the 2 subjects, only 1 subject developed grade 1 Cytokine Release Syndrome (CRS), and no Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). All grade ≥3 hemocytopenia recovered within 4 weeks post infusion. No new safety risk was identified, and the safety profile was superior compared to that in multiple myeloma indication. Effectiveness: Clinical symptoms continued to improve over 18 months in the 2 subjects. From 3 months after the infusion, patients showed significant improvement in limb strength and vital capacity, and sustained improvement in Myasthenia Gravis-Activities of Daily Living Score (MG-ADL), Quantitative Myasthenia Gravis Score (QMG), Myasthenia Gravis-Quality of Life Score (MG-QOL), and Modified Rankin Score (mRS). No immunomodulatory therapy other than low dose pyridostigmine (90 mg/day and 60 mg/day, respectively) was used during the follow-up period. PK/PD: Eque-cel expanded well after infusion and persisted for a shorter period than that in multiple myeloma patients. Anti-AChR antibodies, anti-Titin antibodies, and anti-MuSK antibodies decreased rapidly and maintained at very low levels in both subjects after infusion. B cells and plasma cells decreased to undetectable levels in both subjects within 2 months after infusion and then recovered gradually. At 18 months post-infusion, the B cells of both subjects had returned to normal levels, with approximately 80% of them being naïve B cells, while plasma cells remained at low levels. This result suggests that the long-term efficacy of CAR-T cell therapy may be related to the reconstitution of B cells with a predominantly naïve phenotype and the continued clearance of plasma cells. The principal investigator of this study, Prof. Wei Wang of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, said "Myasthenia Gravis has a long course, is difficult to cure, and is prone to recurrence. Current treatment with traditional medications, although is able to improve symptoms of Myasthenia Gravis to a certain extent, is deficient in terms of disease control and long-term safety, and there is an urgent need for patients to have a better clinical outcome and treatment modality. In our study, it is gratifying to see that BCMA CAR-T cell therapy can prevent MG disease progression and show signs of reversal of the disease, which is expected to change the MG treatment landscape and bring hope for a cure to patients." In addition to the results of this published study, IASO Bio and a team of investigators continue to explore the safety and efficacy of Equecabtagene Autoleucel in the treatment of other antibody-mediated autoimmune diseases, including optic neuromyelitis optica spectrum disorders (NMOSD), Immune-Mediated Necrotizing Myelopathy (IMNM), and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), with an aim to change the landscape of treatment for autoimmune diseases. 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, curable, and affordable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit or . SOURCE IASO Bio