On March 10, 2023 Huihe Biotechnology (CytoCares) reported that its CC312 was approved for clinical trial license by the NMPA (Acceptance number: CXSL2200621), the indication is relapsed/refractory CD19-positive B-cell malignant hematological tumors (Press release, CytoCares, MAR 10, 2023, View Source [SID1234635271]). CC312 is TriTE independently developed by Huihe Biotech. The first product of the platform is also the first trispecific antibody based on CD28 costimulatory signal to be clinically approved in China and the third in the world. This is another milestone after CC312 obtained FDA clinical implicit approval on May 14, 2022, marking the product entering the clinical research stage in China and the United States.

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CC312 is Huihe Biotechnology’s first TriTE-basedTM(Tri-specific T-cell Engager) technology platform independently developed project with independent intellectual property rights. Full activation of T cells requires the synergistic effect of two stimulatory signals, including the first stimulatory signal acting on the CD3/TCR complex, and the costimulatory signal acting on receptors such as CD28 or 4-1BB. Among them, the loss of any signal may lead to incomplete activation of T cells or incompetence or apoptosis after activation. TriTETMThe platform is based on the "dual signal" activation mechanism of T cells and uses co-stimulation signals as the "amplifier" of the first stimulation signal to achieve sustained and sufficient activation of T cells.

CC312 is composed of three single-chain variable region fragments (scFv) targeting CD19, CD3 and CD28 antigens . The three functional domains are connected by a flexible fragment and an IgD hinge region fragment. The T T receptor mediated by the antibody molecule of this structure The immune synapse formed between cells and target cells is closest to the immune synapse mediated by TCR and MHC complexes under natural conditions. By targeting the CD19 functional domain, T cells are precisely directed to tumor cells, and then T cells are fully activated through CD3xCD28 dual stimulation activation signals. Activating T cells with a "dual signal" regulatory mechanism has a longer-lasting activation effect on effector cells and can induce T cells to differentiate into memory T cells. CC312 also has strong tumor suppressive activity at low dosing frequency, thereby Can improve clinical dosing patterns.

Amgen’s blinatumomab (trade name Blincyto) targets CD3xCD19, which is not only expensive, but also requires continuous intravenous infusion for 4 weeks. The administration mode is very inconvenient. CC312 (CD19xCD3xCD28) has shown good pharmacological properties, bioavailability, and safety in preclinical studies for hematomas. As well as effectiveness and longer half-life , it is an upgraded version of the CD19xCD3 dual antibody and has clinical substitution. As an antibody-based version of CAR-T, CC312 has unique advantages in terms of patient compliance and accessibility. It combines the advantages of CAR-T, monoclonal antibodies, and dual antibodies, and has great potential to replace CAR-T therapy.

Dr. Zhu Huaxing, founder and chairman of Huihe Biotechnology, said "The CC312 project has obtained clinical trial research approval from NMPA, which is a major milestone for Huihe Biologics. As China’s first triple-antibody drug based on a dual-signal activation mechanism to obtain IND approval from China and the United States, it has broken the boundaries of foreign new drug development. We are very proud of our monopoly position. We will fully promote the phase I clinical research of CC312 and benefit more subjects as soon as possible. Huihe will also continue to uphold the principle of "continuous innovation, benefiting the people, working together with one heart, and embracing all rivers." The concept of providing more, better and more affordable new drugs for clinical practice and patients."