Business

Innovative Challenger beyond
Immunotherapeutics

CB303

We challenge a high therapeutic effect with the cell-specific
therapeutic agents (CAR-T) specialized in solid cancer.

CB303 is a project combining the CentricsBio's unique anti-cancer target with the latest technology from the immune cell therapy CAR-T (chimeric antigen receptor-T cell). CAR-T is a therapeutic drug for immune cells that have been spotlighted as a 'living drug' due to its superior target-specific attack ability and no need for continuous administration, unlike conventional anticancer drugs. It is a next-generation targeted therapeutic anticancer drug that minimizes side effects caused by drugs and maximizes attack power by taking out the patient's immune cells and then manipulating them to fight cancer cells specifically through activation, proliferation or genetic recombination technology.

In 1989, the first generation of CAR-T was first created by Dr. Zelig Eshhar and colleagues, but due to CAR-T's lack of responsiveness to antigen, it has not been clinically successful for more than 20 years. Later generations added antibodies that specifically recognize the malignant B-cell CD19. In addition, the stimulation signal domain was added to amplify the T cell response, resulting in an excellent growth rate in the body. In the third generation, two extra-stimulatory domains were added, enabling efficient cell proliferation and longer duration in the body with fewer CAR-T doses. Recently, the 4th generation CAR-T, which can secrete cytokines, has also been developed, and more than 500 various studies have been conducted in the US and China to increase the attack on cancer cells.

Novartis received permission from the FDA in August 2018 for the Kymriah, the CAR-T cell therapeutics that targeting lymphocytes that possesses CD19 antigen on the surface of T cells which developed by taking a patient's T cell at the manufacturing center, for the treatment of refractory or recurrent B-cell proliferative acute lymphocytic leukemia under the age of 25. Subsequently, Gilead's Yescarta joined the CAR-T market with FDA approval.

Yescarta is a widespread giant B-cell lymphoma therapeutic, unlike Kymriah, which is a treatment for recurrent refractory acute lymphocytic leukemia. However, both drugs target CD19, the B-cell surface antigen to treat blood cancer.

As described above, CAR-T has no remarkable efficacy in clinical practice due to its inadequate reactivity to cancer cells stemming from the immunosuppressive microenvironment including T cell deactivation factors secreted by tumor tissues in solid cancers such as breast cancer and lung cancer. T-cells have a limit of development, a side effect called cytokine syndrome, which is toxic due to excessive secretion of immune active substances. To overcome this problem, CentricsBio is developing a CB303 project that combines a new immune checkpoint inhibitor, CB301, and CAR-T. CB303 is a new immune cell therapy that targets CB301 antigens expressed on various cancer surfaces, overcomes the immunosuppressive microenvironment of solid cancer, induces T cell activation (similar to the mechanism of PD-1 / PD-L1 target immunosuppressive drugs), and directly kills cancer cells and is highly reactive in solid cancer.

CB303 overcomes the problems of CAR-T by combining the latest immune cell therapeutic technology called CAR-T and a new anticancer target called CB301. As a targeted therapeutic drug for solid cancer, it overcomes the immune suppression environment of cancer cells by using the mechanism of action of immune checkpoint inhibitor and utilizes the characteristics of CB301 antigen expressed in various cancer cells. Thus, it can be applied as a "universal CAR-T" rather than a specific cancer. Thus, CB303 opens up a new paradigm for targeted therapies for solid cancers and will be the best-in-class personalized medicine therapies in the global CAR-T market with immune cell therapies with minimal side effects and maximized efficacy.

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