The Phase Ib/II clinical study of IMM01 combined with PD-1 antibody in the treatment of relapsed and refractory malignant tumors completed the first patient enrollment and administration
On May 17, 2022, ImmuneOnco Biopharmaceuticals (Shanghai) Co., Ltd. (hereinafter referred to as "ImmuneOnco") announced the FPI in the Phase Ib/II clinical study of first domestic SIRPα-Fc fusion protein targeting human CD47 (project number: IMM01) combined with PD-1 antibody for relapsed and refractory malignant tumors (clinical research project number: IMM01-04). The first subject was enrolled and dosed successfully. The patient was a 56-year-old male with squamous cell esophagus carcinoma and the first infusion was completed without any adverse events reported.
The preliminary data from phase I of IMM01 is promising and encouraging. At the lower doses, it has benefited some patients with advanced lymphoma with a good safety profile. These clinical manifestations benefit from our differentiated design of the IMM01 molecule. IMM01 does not bind to human erythrocytes at all so as to avoid the "antigen sink effect", and it demonstrates low antigenicity without ADA. Its smaller molecule weight (only half of IgG molecule) guarantees better tissue permeability and bioavailability. In preclinical in vivo efficacy experiments, IMM01 was tested in combination with other targeting and immunotherapy drugs showing strong tumor suppressive activity and combined drug potential against solid tumors.
PD-1 antibody demonstrated superior curative effect on a variety of tumors. The PD-1 immunotherapy was limited by the content of T cells in tumor tissue (such as "cold tumor"), most patients do not have a good response on PD-1 antibody therapy. Macrophages are innate immune cells and born to be antigen-presenting cells. After activation, they can improve the efficacy of PD-1 antibody and maintain the durability of the efficacy through the following ways:
1) Directly phagocytose tumor cells, and present the processed tumor antigens to T cells to induce tumor antigen-specific T cell responses;
2) Release of chemokines (such as CXCL9/CXCL10) to chemotaxis T cells to the tumor tissue, thereby transforming "cold tumors" into "hot tumors" (Figure 1).
Figure 1. Activation of macrophages helps to overcome low response rate and dug resistance of PD-1 antibody therapy
Dr. Tian, Wenzhi, founder, chairman and CEO of ImmuneOnco, said:"I am very pleased to see that the clinical study of our IMM01 project combined with PD-1 antibody in the treatment of relapsed and refractory malignant tumors has completed the first patient enrollment and administration. Preclinical studies have shown that IMM01 combined with PD-1 antibody has a strong synergistic effect. We have reason to believe that IMM01 combined with PD-1 antibody will have superior clinical performance and it will bring good news to the majority of cancer patients."
Figure 2. Preclinical in vivo efficacy study of IMM01 combined with PD-1 antibody
IMM01 is a new-generation immune checkpoint inhibitor with independent intellectual property rights developed based on "mAb-Trap" technology of ImmuneOnco. It targets the immunomodulatory target CD47 and activates the phagocytosis of tumor cells by macrophages, and present the phagocytosed tumor antigens to T cells, thereby exerting a powerful tumor immunotherapy effect. The IMM01 perfectly solves the major obstruction of CD47 targeting drug development. Imm01 has been approved for invention patents in China, Japan and the United States.