Kunstone Biotech, Nanjing Gulou Hospital, and Jiangsu Institute of Cell Therapy Drug Research Enter Strategic Clinical Collaboration on CAR-M for Autoimmune Diseases

Sep 22, 2023 11:02 CST Updated 11:02

Rock Roc Biotechnology

Macrophage Chimeric Antigen Receptor Therapy Developer

On September 21, 2023, ROC ROCK Biotechnology, Nanjing Drum Tower Hospital, and the Cell Therapy Drug Research Institute of Jiangsu Industrial Technology Research Institute signed a strategic clinical cooperation agreement for CAR-M targeted therapy in autoimmune diseases. This collaboration represents a powerful partnership between the three parties. Chairman Jianguo Yin of Suzhou Industrial Park Biotechnology Development Co., Ltd. witnessed this historic moment. This strategic cooperation marks the first time that macrophage drugs have entered the field of treating autoimmune diseases on a global scale, bringing new hope for the treatment of autoimmune diseases.

(Third from the left: Professor Shi Ming, Executive Director of the Jiangsu Provincial Engineering Laboratory for Tumor Biotherapy; Fourth from the left: Dr. Yin Jianguo, Chairman of Suzhou Industrial Park Biotech Development Co., Ltd.; Center: Dr. Yin Xiushan, CEO of ROC ROCK Biotechnology; Fourth from the right: Professor Sun Lingyun, Director of the National Regional Medical Center at Nanjing Drum Tower Hospital and President of the Second Affiliated Hospital of Anhui Medical University)

Autoimmune Diseases: A Major Category of Illness in Urgent Need of New Therapies

Autoimmune diseases are a group of conditions in which the immune system abnormally attacks the body's own tissues and organs, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, etc. These diseases often cause long-term suffering for patients, severely impacting their quality of life. Current treatments can usually only control symptoms but not cure the diseases, and they come with a range of side effects.

Systemic lupus erythematosus (SLE) is a heterogeneous chronic autoimmune disease. The presence of various autoantibodies represented by antinuclear antibodies (ANA) in the serum and multi-system involvement are the two main clinical features of SLE. Traditional treatments include immunosuppressants, biologics, and antimalarial drugs, which have many limitations and an urgent need for safer and more effective therapeutic approaches.

The Potential of CAR-M Targeted Therapy for Autoimmune Diseases

Professor Sun Lingyun's team from Drum Tower Hospital, Nanjing University, has successfully tackled the global challenge of treating refractory lupus erythematosus after 18 years of relentless efforts, reducing the 5-year mortality rate of this disease from 45% to 16%. The team was the first internationally to carry out allogeneic mesenchymal stem cell therapy for autoimmune diseases such as lupus erythematosus and successfully promoted the application of research results to 35 units inside and outside the province. Since 2007, more than 1,700 cases have been treated with mesenchymal stem cell transplantation without any treatment-related deaths. The effective rate of treating refractory lupus erythematosus can reach about 60%, which is quite remarkable. The team's Phase 1 and Phase 2 clinical studies on the treatment of lupus nephritis using umbilical cord blood mesenchymal stem cell injections were approved in June 2022, and the research is currently proceeding smoothly.

Professor Sun Lingyun

(Leader in Cell Therapy for Lupus Erythematosus in China)

In systemic lupus erythematosus, CD19, as a protein on the surface of B cells, is involved in disease flare-ups. At the same time, CD19 is also a target for several CAR-T therapies currently approved for treating hematological malignancies. In recent years, a team from the University of Erlangen-Nuremberg in Germany has used CD19-targeted CAR-T therapy to treat six lupus patients. So far, no relapse has been observed in the longest-followed patient (17 months), and none of the patients are using any systemic lupus erythematosus medications. This suggests that lupus may be an easier target for CAR-T cell therapy than B-cell tumors.

Professor Ming Shi's team from Xuzhou Medical University, dedicated to the research and development of CAR-T cells and exploratory clinical trials, has completed clinical treatment for over 600 cancer patients. The team developed humanized CD19 CAR-T and BCMA CAR-T, pioneered the use of CD19 plus BCMA dual-target CAR-T cell therapy for advanced multiple myeloma, and expanded the indications of CAR-T by utilizing the B-cell depletion effect of dual-targeted CAR-T cells to treat refractory autoimmune diseases in neurology, such as chronic Guillain-Barré syndrome, neuromyelitis optica, and myasthenia gravis. In January 2021, the team successfully cured a Pakistani patient using CD19 CAR-T + BCMA CAR-T combination therapy for multiple myeloma. In 2022, the 21.3-month long-term follow-up results of this therapy were published in the top international academic journal *J Clin Oncol*. Among the 62 infused patients, the objective response rate (ORR) was 91.9%, with complete or better responses (sCR+CR) at 59.6%, and 77% (43/56) of patients achieved MRD negativity, showing good long-term safety. The efficacy was superior to the two marketed BCMA CAR-T products.

Professor Shi Ming

(Executive Director of the Jiangsu Provincial Tumor Biotherapy National-Local Joint Engineering Laboratory)

Macrophages, as the main force of innate immunity, possess functions such as phagocytosis, antigen presentation, and secretion. They are the first line of defense in the immune system against pathogens and the primary executors in phagocytosing dead and senescent cells to maintain the body's dynamic balance. Engineered macrophages hold broad prospects and immense therapeutic potential for treating tumors and systemic diseases. As a leader in CAR-M therapy in China, ROC ROCK Biotechnology has already demonstrated forward-looking results in treating solid tumors such as breast cancer, ovarian cancer, and gastric cancer, showcasing the significant therapeutic possibilities of CAR-M in solid tumors. Dysfunctional B cells are the culprits behind autoimmune diseases like lupus erythematosus. There are multiple ways to eliminate these B cells, including commonly used lymphodepletion. However, due to insufficient depth and incomplete lymphodepletion, relapses often occur. By engineering macrophages to precisely identify dysfunctional B cells hidden deep within various tissues that cannot be eliminated, we aim to achieve the treatment of autoimmune diseases and lupus erythematosus.

(CAR-M Cells)

Strategic Clinical Collaboration: Entering a New Era

This cooperation agreement marks that ROC ROCK Biotechnology, Nanjing Drum Tower Hospital, and the Cell Therapy Drug Research Institute of Jiangsu Industrial Technology Research Institute have entered an internationally uncharted territory in the field of cell therapy. It also represents a new phase driven by original research in China's cell therapy sector. This collaboration is also an active attempt at multi-party industry-academia-research cooperation in the Yangtze River Delta region. By pooling the expertise and resources of all parties, it aims to advance scientific research and progress in the field of autoimmune diseases, accelerate the development and clinical application of CAR-M targeted therapy, and bring more effective treatment options to patients.

This collaboration will undoubtedly deepen the cooperation and exchange among the three parties in the field of immune diseases, advancing towards a higher level and higher quality. Taking this as a new starting point, we will work together with one heart to create a new situation of "win-win cooperation."

(Negotiation and Communication)

Introduction to Professor Sun Lingyun from Nanjing Drum Tower Hospital

Sun Lingyun, Chief Physician, Ph.D., Professor, and Doctoral Supervisor. Currently serves as the Director of the National Regional Medical Center at Nanjing Gulou Hospital and the President of the Second Affiliated Hospital of Anhui Medical University. He has previously served as the Vice Chairman of the Chinese Rheumatology Association and the Chairman of the Jiangsu Rheumatology Association. He currently holds positions such as the Vice President of the Rheumatology and Immunology Branch of the Chinese Medical Doctor Association, Honorary Chairman of the Jiangsu Rheumatology Association, and Executive Director of the Jiangsu Immunology Society. He has studied in Italy, Japan, the UK, and Australia and enjoys a special allowance from the State Council. Professor Sun Lingyun was the first to establish a laminar flow ward in the rheumatology department in China and conducted pioneering work internationally in 2007.Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation for the Treatment of Lupus Erythematosus`, Hosting the First National Conference for Young and Middle-aged Rheumatology Backbone Physicians and the 11th National Rheumatology Academic Conference.`Specializing in Lupus Erythematosus, Sjögren's syndrome, arthritis, scleroderma, myositis, vasculitis, spondyloarthropathy, hematopoietic stem cell transplantation, allogeneic mesenchymal stem cell transplantation, and other fields.

Introduction to Professor Ming Shi from the Jiangsu Cancer Biotherapy Research Institute

Shi Ming, Ph.D., Professor, Doctoral Supervisor. Currently serves as the Executive Director of the National and Local Joint Engineering Laboratory for Tumor Biotherapy; Executive Director of the Cell Therapy Drug Research Institute at the Yangtze River Delta National Innovation Center; Executive Director of the Jiangsu Province Cell Therapy Drug Industrial Innovation Center; and Director of the Jiangsu Province Tumor Biotherapy Engineering Laboratory. He is primarily engaged in the research and development of CAR-T cells and exploratory clinical trials, having closely collaborated with clinical departments to complete treatment for over 600 cancer patients, achieving internationally advanced levels of efficacy. He has led six projects under the National Natural Science Foundation of China, one sub-project of a National 863 Program, one sub-project of a National Major New Drug Creation Project, and one key R&D plan of Jiangsu Province, accumulating over 15 million yuan in research funding. As the first or corresponding author, he has published 29 SCI papers, co-authored two foreign academic monographs, translated two academic monographs, and obtained five authorized national invention patents. He has won one first prize and one third prize for military scientific and technological progress, and one third prize from the Chinese Anti-Cancer Association Science and Technology Award.

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