Pharma Focus Asia

Biocytogen and CtM Bio Make Noteworthy Progress in Collaborative Development of TCR-Mimic Antibody-Based Multi-Specific T Cell Engager Targeting WT1/HLA-A02

Thursday, December 28, 2023

Biocytogen Pharmaceuticals (Beijing) Co., Ltd. ("Biocytogen", HKEX: 02315) and CtM Biotech (Shanghai) Co., Ltd. ("CtM Bio") have reported significant advancements in the development of a tri-specific T cell engager targeting an intracellular protein. Achieving this progress within just one year of collaboration, the companies have successfully identified a T cell engager (WT1xCD3x4-1BB tri-specific antibody) designed for WT1 with exceptional preclinical anti-tumor activities against both hematological malignancies and solid tumors. This engager includes a T co-stimulatory signal, giving it best-in-class properties and a first-in-class potential. The preclinical data for this development has been accepted for presentation at the upcoming 2024 AACR annual meeting.

WT1 (Wilms' tumor gene 1) is an intracellular protein highly expressed in certain cancer cells compared to normal tissues, making it an attractive target for cancer immunotherapy. Biocytogen used its RenTCR-mimicTM mice and advanced screening platforms to generate WT1 antibodies with superior specificity and high affinity to the HLA/peptide complex. CtM Bio's T cell engager technology was then applied to engineer these antibodies, aiming to overcome T cell over-activation toxicity and prevent T cell exhaustion, resulting in highly effective, safe, and controllable multi-specific engagers.

Dr. Yuelei Shen, President and CEO of Biocytogen, expressed satisfaction with the rapid progress, stating, "Our collaborative efforts with CtM Bio have led to the identification of novel immunotherapies targeting WT1. This development validates CtM Bio's advanced T-cell engager technology and our expertise in discovering fully human TCR-mimic antibodies against intracellular targets. We anticipate advancing this preclinical candidate into clinical trials soon, offering 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, highlighted the synergy between Biocytogen's antibody discovery capabilities and CtM Bio's expertise in immune cell engagers, expressing enthusiasm for continued collaboration. Together, they aim to usher in a new era of therapies targeting intracellular tumor antigens, expanding the applications of T cell engagers for solid tumor treatment, and providing new opportunities for cancer patients.

Biocytogen's TCR-Mimic Antibody Discovery Platform focuses on generating fully human antibodies to intracellular targets presented on the cell surface. Leveraging proprietary RenTCR-mimicTM mice and specialized immunization protocols, the platform aims to produce TCR-mimic (TCRm) antibodies with high specificity and affinity, overcoming tumor immune escape. Fully human antibody sequences obtained from this platform can support the development of various therapies.

CtM Bio's T-cell Engager Platform, named TOPAbody, addresses the limitations of existing T cell engagers by introducing T-cell co-stimulatory signal 4-1BB. This platform enhances T cell cytotoxicity with minimal side effects, prolongs T cell lifespan, and promotes T cell infiltration into tumors. Several products from this platform have shown promising anti-tumor activity, particularly for immunologically "cold" tumors that do not respond to PD-1 treatment.



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