Hengrui Yuanzheng's MASCT-I Cell Therapy Receives Approval for Phase II Clinical Trial as First-Line Treatment for Advanced Soft Tissue Sarcoma

Oct 30, 2023 08:23 CST Updated 08:23

HRYZ

Immune Cell Therapy Developer

On October 29, Hengrui Yuanzheng announced that it had received the official drug clinical trial approval notice from the China National Medical Products Administration (NMPA), agreeingIts Multi-Antigen Autologous Immune Cell Injection (MASCT-I)LaunchCombination with First-line Chemotherapy for the Treatment of Advanced Soft Tissue SarcomaClinical trials.

Soft tissue sarcoma is a malignant tumor of mesenchymal origin, primarily derived from the mesoderm, with some originating from the neuroectoderm, and mainly includes muscle, fat, fibrous tissue, blood vessels, and peripheral nerves.Soft Tissue SarcomaThe most common subtypes include undifferentiated pleomorphic sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, and so on.

MASCT-I is a cell therapy product developed by Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd., and its active ingredients includeMature autologous dendritic cells (referred to as "DC cells") loaded with multiple tumor-associated antigens and the aforementioned DC cell-activated and expanded autologous effector T lymphocytes (referred to as "T cells"),In clinical use, tumors are eliminated through sequential treatment with both. Among them, DC cells are derived from monocytes isolated from the peripheral blood of cancer patients. After being loaded with various tumor-associated antigens in vitro, the antigen epitope peptides are presented on the surface of DC cells via MHC class I/II molecules.These multi-antigen-loaded DC cells, after subcutaneous injection, present antigen epitopes to CD8 and CD4 T cells in the patient's lymphoid tissue, activating them into effector T cells with anti-tumor effects, which then eliminate tumors through cytotoxic action.

In addition, a portion of the multi-antigen-loaded DC cells were further co-cultured with the patient's peripheral blood mononuclear cells (PBMCs) to activate and expand tumor-specific T cells in the PBMCs, thereby obtaining a large number of effector T cells with anti-tumor effects in vitro. These effector T cells were intravenously infused back into the patient's body, entering the tumor tissue through blood circulation to further exert their tumor-killing effects.

MASCT-I was approved in China in 2018.Monotherapy for Malignant Solid TumorsClinical research. Currently, MASCT-I monotherapy has completed Phase 1 clinical research, withPatients with urothelial carcinomaA Phase 2 clinical study for the subjects is currently underway.

The clinical study approved for Hengrui Yuanzheng this time is: "Evaluation of MASCT-I in Combination with Doxorubicin and Ifosfamide"First-line treatment for patients with advanced soft tissue sarcomaThe efficacy and safety of a randomized controlled, multi-centerPhase 2 Clinical Study". Hengrui Yuanzheng stated in the press release that it will actively promote the progress of this clinical study.

Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd. was founded in Shanghai in 2015 by Jiangsu Hengrui Pharmaceutical Group and Shenzhen Yuanzheng Cell Medical Technology Co., Ltd. It is an immunotherapy cell treatment enterprise in China that focuses on solid tumors, maintaining both domestic leadership and international synchronization. The company has developed multiple product pipelines for solid tumor patients, including MASCT, TCR-T, and TCR bispecific antibodies. Among them, the MASCT pipeline is currently the world's first multi-target cell therapy product for solid tumors to have received clinical approval and has entered phase II clinical trials. The TCR-T pipeline isolates TCRs with optimal affinity from tumor patients who have benefited from years of MASCT clinical treatments, accumulating a vast amount of TCR data based on Asian population HLA typing, offering significant advantages over TCR products based on European and American population HLA typing. The TCR bispecific antibody is a standardized product that can be mass-produced, providing better cost-efficiency compared to customized cell therapy products.

Team led by the founder of Hengrui Pharmaceutical Group

Jiangsu Hengrui Pharmaceutical Group is the controlling shareholder of Hengrui Yuanzheng, and Hengrui Yuanzheng is also the only company in the cell therapy field that Hengrui Group has invested in. Mr. Sun Piaoyang, the founder of Hengrui Group, serves as the chairman of Hengrui Yuanzheng; Mr. Li Kejian, the general manager of Hengrui Yuanzheng, served as the vice president of Hengrui Pharmaceutical; Mr. Zhou Xiangjun, the founder and chief scientist, holds a medical doctorate from the United States, was a postdoctoral fellow at Stanford University, and previously served as a professor at Shanghai Jiao Tong University School of Pharmacy; Ms. Han Yanyan, the vice general manager, is the head of drug discovery, with a doctorate from the Medical Faculty of Ludwig Maximilian University of Munich, Germany, and completed her postdoctoral studies at the affiliated Right Bank Hospital of Technical University of Munich, Germany, with extensive experience in tumor immunology research and years of expertise in cellular immunity and molecular immunology; Ms. Ma Yifan, the vice general manager, is the head of process development, holding a Ph.D. in life sciences from Pennsylvania State University, and previously served as a researcher and doctoral supervisor at the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, and as a reviewer for major projects under the National Science Foundation of China (NSFC) and the Ministry of Science and Technology; Ms. Li Xiaoshuang, the chief medical officer and vice general manager, is the clinical lead, with a master's degree in medicine from the United States, nearly 30 years of senior management experience at foreign pharmaceutical companies such as Merck, Amgen, Novartis, and Boehringer Ingelheim, and rich experience in Phase I to Phase IV clinical research and management; Ms. Li Jin, the vice general manager, is the production lead, with a master's degree from the Academy of Military Medical Sciences of China, and conducted research on cellular immunotherapy technology at the University of London; the core executives of the company all come from prestigious universities both domestically and abroad, with abundant relevant industry experience. The company maintains balanced capabilities across R&D, manufacturing, regulatory submission, commercialization, and other key stages.

Clinical cooperation with multiple leading cancer hospitals

Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd. has collaborated with several leading hospitals in the oncology field, including Sun Yat-sen University Cancer Center, Zhongshan Hospital Affiliated to Fudan University, Fudan University Shanghai Cancer Center, Peking University Cancer Hospital, Shanghai Sixth People's Hospital, Zhejiang Cancer Hospital, and First Affiliated Hospital of Sun Yat-sen University, to conduct registered clinical trials and investigator-initiated clinical studies. These efforts have secured an advantageous academic position and laid a solid foundation for future product commercialization.

Hengrui Yuanzheng MASCT Pipeline

MASCT is the abbreviation for Multi-Antigen Stimulated Cell Therapy Injection, a multi-antigen autologous immune cell injection, whose active ingredients include mature autologous dendritic cells (referred to as "DC cells") loaded with 15 tumor-associated antigens and autologous effector T lymphocytes (referred to as "T cells") activated and expanded by the aforementioned DC cells.

MASCT is a series of autologous immune cell therapy technology products for solid tumors, containing mature DC cells loaded with multiple antigen peptides and effector T cells expanded and activated in vitro, which eliminate tumors through sequential treatment. Among them, DC cells are derived from monocytes isolated from the peripheral blood of cancer patients and are loaded with 15 tumor-associated antigens in vitro. The epitope peptides of these antigens are presented on the surface of DC cells via MHC class I/II molecules. After subcutaneous injection, these multi-antigen-loaded DC cells present the antigen epitopes to CD8 and CD4 T cells in the patient's lymphoid tissue, activating them into effector T cells with anti-tumor effects, thereby eliminating tumors through cytotoxic action. Additionally, some of the multi-antigen-loaded DC cells are further co-cultured with the patient’s peripheral blood mononuclear cells (PBMCs) to activate and expand tumor-specific T cells within the PBMCs, obtaining a large number of effector T cells with anti-tumor effects in vitro. These effector T cells are intravenously infused back into the patient’s body, enter the tumor tissue through blood circulation, and further exert their tumor-killing effects.

MASCT can enhance immune response and extend the duration of benefits from standard first-line chemotherapy in cancer patients. It does not involve genetic modification of T-cells, features mature technology, low toxicity, and high safety. Excellent safety and efficacy data were obtained from Phase I clinical trials, and approval for Phase II clinical trials was granted in December 2021. The Phase I clinical trial indication was malignant solid tumors, with the first approved indication for Phase II being advanced urothelial carcinoma. Multiple indications will be applied for future clinical trials.

InSource: Zijin Harbor Capital, Medicine Viewpoint, Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd., Official Account "Cell and Gene Therapy Field"

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