Hengrui Yuanzheng Successfully Completes First TCR-T Cell Infusion in Phase I Trial for HPV18+ Solid Tumors

Oct 28, 2023 09:30 CST Updated 09:30

HRYZ

Immune Cell Therapy Developer

Recently,HengRuiyuan Zheng (Shanghai) Biotechnology Co., Ltd.Announcement: The Phase I open-label clinical trial of autologous T cells transduced with a T-cell receptor (TCR) targeting HPV18E7 (HRYZ-T101) for the treatment of human papillomavirus (HPV)-related solid tumors successfully completed the first participant's cell infusion on October 25, 2023. To date, the first participant is in good condition, with no observed related adverse reactions such as cytokine release syndrome or neurotoxicity. The completion of the first participant’s cell infusion marks a milestone for the TCR-T pipeline development at Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd. and for the treatment of HPV-related solid tumors. Participant recruitment for this clinical study is ongoing.

HRYZ-T101 Injection is the second IND-approved product by Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd., and also its first TCR-T cell therapy product. TCR-T is a type of TCR gene-modified T-cell technology that enhances the ability of T cells to recognize and kill tumor cells by expressing tumor-specific TCR chains in T cells. Unlike CAR molecules, which can only recognize membrane proteins, TCR molecules are capable of identifying intracellular proteins presented by tumor cells. This feature gives TCR-T technology greater advantages and potential in the treatment of solid tumors and has become a hot topic in the current field of immune cell therapy.

Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd. has independently developed a TCR screening technology platform based on reverse gene engineering (Reverse Genetic Engineering of TCR-T, ReGET), which can rapidly and efficiently isolate TCRs with optimal affinity from tumor patients who benefit from immunotherapy. The platform has accumulated a large amount of TCR data based on HLA typing of the Asian population, which is used for the research and development of anti-tumor TCR-T products, offering significant advantages over TCR products based on HLA typing of European and American populations.

In addition, in May this year, Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd. completedCRound financing exceeded2Hundred Million Yuan, Zijin Harbor Capital continued to increase its investment as the main investor in this round. Other major investors in this round include Hengrui Pharmaceutical Group, Zhongke Venture, etc. Hengrui Yuanzheng (Shanghai) Biotechnology Co., Ltd.2020Year CompletedA+Round of financing andBTwo rounds of financing, and2021Built the headquarters base and the Yangtze River Delta regional cell preparation center in Songjiang, Shanghai.

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 a leading domestic position and international synchronization. The company has developed multiple product pipelines for patients with solid tumors, 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 extensive TCR data based on Asian population HLA typing, which provides 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, offering superior cost and efficiency compared to customized cell therapy products.

Team led by the founder of Hengrui Medicine 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 general manager of Hengrui Pharmaceutical; Dr. 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 the School of Pharmacy of Shanghai Jiao Tong University; Ms. Han Yanyan, the vice general manager and head of drug discovery, holds a doctorate from the Medical Faculty of Ludwig-Maximilians-Universität München in Germany and completed her postdoctoral studies at the Klinikum rechts der Isar, Technical University of Munich, with years of experience in cancer immunology research, accumulating extensive expertise in cellular and molecular immunology; Ms. Ma Yifan, the vice general manager and head of process development, earned her 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.NSFCAnd a major project review expert of the Ministry of Science and Technology; Chief Medical Officer and Vice President Ms. Li Xiaoshuang as the clinical leader, Master of Medicine from the United States, with nearly30Years of executive experience at foreign pharmaceutical companies such as Merck, Amgen, Novartis, and Boehringer Ingelheim, with extensiveI Due DateIVClinical research and management experience; Vice General Manager Ms. Li Jin is the production head, a master's graduate from the Academy of Military Medical Sciences in China, and has conducted research on cellular immunotherapy technology at the University of London; the company’s core executives all hail from prestigious universities both within and outside China, possessing extensive industry-related experience. The company demonstrates balanced capabilities across R&D, production, regulatory submission, and commercialization.

Collaborate clinically 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 the First Affiliated Hospital of Sun Yat-sen University, to conduct registered clinical trials and investigator-initiated clinical studies. This positions them advantageously in academia and provides a solid foundation for future product commercialization.

Hengrui YuanzhengMASCTPipeline

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.

MASCTIt is a series of autologous immune cell therapy technology products for solid tumors, containing mature cells loaded with multiple antigen peptides.DCEffects of Cell and In Vitro Activation ExpansionTCells, to eliminate tumors through sequential treatment of the two.Among them,DCCells are derived from monocytes isolated from the peripheral blood of tumor patients and loaded in vitro with15After implanting tumor-associated antigens, the antigen epitope peptides are passed throughMHC I/IIClass molecules presented toDCCell surface.These multi-antigen-loadedDCAfter subcutaneous injection, the cells present antigen epitopes to the lymphoid tissues in patients.CD8AndCD4 TCells, activating them to become effectors with anti-tumor effectsTCells, thereby eliminating tumors through cytotoxic effects.In addition, a part of multi-antigen loadingDCCells were also co-cultured with patient peripheral blood mononuclear cells (PBMCs) Further co-culture, activation and expansionPBMCsTumor specificity inTCells, thereby obtaining a large number of effector cells with anti-tumor effects in vitroTCell.This part of the effectTCells are intravenously infused into the patient's body, enter the tumor tissue through blood circulation, and further exert their tumor-killing effects.

MASCTCan enhance immune response and extend the duration of benefit after standard first-line chemotherapy for cancer patients;Not involvedTGene modification of cells, with relatively mature technology, low toxicity, and high safety;Pipeline Phase I clinical safety and efficacy data are excellent,2021Year12Received Phase II clinical approval in the month;Phase I clinical indications are malignant solid tumors, and the first approved indication for Phase II clinical trials is advanced urothelial carcinoma. Multiple indications will be applied for in the future.