Beijing, China and Shanghai, China, December 27, 2023 – Biocytogen Pharmaceuticals (Beijing) Co., Ltd. (“Biocytogen”, HKEX: 02315) and CtM Biotech (Shanghai) Co., Ltd ("CtM Bio") today jointly announce that the development of a tri-specific T cell engager for an intracellular target achieved milestone progress. In just one year since the start of the collaboration, the companies have identified a WT1/HLA-A02-specific T cell engager (WT1xCD3x4-1BB tri-specific antibody) with outstanding preclinical anti-tumor activities for both hematological malignancies and solid tumors. The incorporation of the T co-stimulatory signal for WT1-targeting T cell engager further gives it the best-in-class properties and first-in-class potential. Its preclinical data has been accepted for presentation at the upcoming 2024 AACR annual meeting.
WT1 (Wilms’ tumor gene 1) is an intracellular protein highly enriched in certain cancer cells compared to normal tissues, making it an attractive tumor target for cancer immunotherapy. To identify novel WT1-targeting antibody-based therapeutics, Biocytogen harnessed its RenTCR-mimicTM mice and high-throughput in vivo and in vitro screening platforms to successfully generate WT1 antibodies with superior specificity and high affinity to the HLA/peptide complex. These antibodies were further engineered using CtM’s state-of-the-art T cell engager technology, which is specifically designed to overcome T cell over-activation toxicity and prevent T cell exhaustion, leading to highly effective, safe and controllable multi-specific engagers.
Dr. Yuelei Shen, President and CEO of Biocytogen, said, “Our collaborative efforts with CtM Bio have progressed rapidly, resulting in the identification of novel immunotherapies targeting WT1. This rapid and effective development of multi-specific T cell engagers undoubtedly validates CtM Bio’s advanced T-cell engager technology, along with our expertise in discovering fully human TCR-mimic antibodies against intracellular targets. We anticipate advancing this preclinical candidate into clinical trials soon, providing treatment options for patients with acute myeloid leukemia, ovarian cancer, and various solid tumors.”
Dr. Lei Fang, Vice President of Lepu Biopharma and CEO of CtM Bio, said, “The combination of Biocytogen’s streamlined fully human antibody discovery capabilities and CtM Bio’s deep understanding of immune cell engagers have greatly accelerated our development of differentiated T cell engagers targeting WT1. We look forward to continued collaborations to further develop this candidate and initiate clinical trials. Together, we aim to usher in a new era of therapies targeting intracellular tumor antigens and broaden the applications of T cell engagers for the treatment of solid tumors, which will ultimately offer new opportunities for cancer patients.”
About the TCR-Mimic Antibody Discovery Platform
Biocytogen’s TCR-Mimic platform focuses on the discovery of fully human antibodies to intracellular targets that are presented on the cell surface by MHC class I molecules. Leveraging proprietary RenTCR-mimicTM (HLA/RenMab) mice and specialized immunization protocols, Biocytogen’s platform is designed to generate TCR-mimic (TCRm) antibodies that are highly specific for peptide/HLA complexes and not HLA itself. Subsequently, Biocytogen’s high-throughput antibody screening platform aims to swiftly identify TCR-mimic antibodies with higher specificity and affinity than endogenous TCRs derived from patients to overcome tumor immune escape. Currently, antibody hits for multiple intracellular targets, including TAAs, cancer-testis antigens, mutated protein antigens, and viral protein antigens, are being evaluated in vivo and in vitro. Fully human antibody sequences obtained from the TCR-mimic platform can empower the development of T cell engagers, bispecific/multispecific antibodies, and CAR-T therapies.
About the T-cell Engager Platform
T-cell engagers are typically bispecific antibodies with one targeting tumor-associated antigens (TAAs) and the other activating CD3 signal on T cells. The mechanisms involve promoting the formation of an immune synapse between T cells and cancer cells, activating T cells to induce the lysis of cancer cells. To overcome the limitations of existing T cell engagers, CtM Bio has developed a unique T cell engager platform called TOPAbody. By introducing T-cell co-stimulatory signal 4-1BB and finely tuning the affinity and activity of each module in the engager, TOPAbody allows for the effective enhancement of T cell cytotoxicity with minimal side effects. TOPAbody prolongs T cell lifespan and promotes T cell infiltration into tumors. Currently, several products from this platform have demonstrated outstanding anti-tumor activity, particularly showing significant promise for immunologically "cold" tumors that do not respond to PD-1 treatment.
Biocytogen (HKEX: 02315) is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Founded on gene editing technology, Biocytogen leverages genetically engineered proprietary RenMice® (RenMabTM/RenLite®/RenNano®/RenTCR-mimicTM) platforms for fully human monoclonal/bispecific/multispecific antibody discovery, bispecific antibody-drug conjugate discovery, nanobody discovery and TCR-mimic antibody discovery, and has established an off-the-shelf library of >400,000 fully human antibody sequences against approximately 1000 targets for worldwide collaboration. As of June 30, 2023, 50 therapeutic antibody and multiple clinical asset co-development/out-licensing/transfer agreements and 42 target-nominated RenMice® licensing projects have been established around the globe, including several partnerships with multinational pharmaceutical companies (MNCs). Biocytogen pioneered the generation of drug target knock-in humanized models for preclinical research, and currently provides a few thousand off-the-shelf animal and cell models under the company’s sub-brand, BioMiceTM, along with preclinical pharmacology and gene-editing services for clients worldwide. Headquartered in Beijing, Biocytogen has branches in China (Haimen Jiangsu, Shanghai), USA (Boston, San Francisco), and Germany (Heidelberg). For more information, please visit http://en.biocytogen.com.cn.
About CtM Bio
CtM Bio, a subsidiary of Lepu Biopharma (2157.HK), is a science-driven biotech company committed to the development of innovative antibody-based therapies that could ultimately address the un-met medical needs. The company’s focus is to integrate its knowledge in immunology and disease biology with the most cutting-edge technology and platforms, aiming to design novel antibodies that could fully unlock the potential of immunotherapy. Lepu Biopharma is China-based global-oriented innovation-driven biopharmaceutical company. The company is committed to innovation, focusing on the discovery, development and commercialization of drug candidates with the first and optimal potential of the same kind in anti-tumor targeted therapy and immunotherapy drugs. The company's mission is to develop safe, effective, and accessible drugs to improve cancer patients’ quality of life and to address huge gaps in medical needs. The company attaches great importance to the continuous construction of commercialization capacity and strives to realize the strong transformation and industrialization capacity from core technology to finished drugs.
Antibody assets and platforms: BD-Licensing@biocytogen.com