On January 29, 2022, SIM0235 (SIM1811-03 injection), a humanized anti-tumor necrosis factor receptor 2 (TNFR2) monoclonal antibody independently developed by Simcere，has obtained the Investigational New Drug (IND) approval issued by the U.S. Food and Drug Administration (FDA), which is intended to be used for clinical trials of advanced solid tumors and cutaneous T-cell lymphoma (CTCL). SIM0235 has obtained the clinical trial approval issued by the National Medical Products Administration, PRC on December 6, 2021.
The tumor necrosis factor receptor 2 (TNFR2) is a member of the tumor necrosis factor receptor superfamily, and is primarily expressed on the surface of tumor cells and suppressive immune cells in the tumor microenvironment, but rarely in normal human tissues or peripheral immune cells. TNFR2 is understood to be a potential driving force for immune escape and tumor proliferation.
SIM0235 is humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets and inhibits TNFR2. The antibody is thereby able to kill associated TNFR2-expressing immune suppressive cells including regulatory T cells (Tregs) and bone marrow-derived suppressor cells, through a process using antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) and other Fc-receptor functions.
Additionally, the molecule can block the activation of TNFR2 by endogenous tumor necrosis factor (TNF), and affect the immunosuppressive function and proliferation mediated by TNFR2 to enhance the body's immune response to tumors. SIM0235 is able to also bind to TNFR2 on the surface of tumor cells and kill the tumor cells directly.
Preclinical studies have shown that SIM0235 has a high level of binding specificity towards TNFR2 and ability to block the activation of the NF-κB signaling pathway, thereby effectively inhibiting the proliferation and function of Treg cells and better regulating the immunity microenvironment. SIM0235 was shown to have a significant killing effect on TNFR2-positive cells in ADCC and ADCP in vitro studies. Several in vivo models have demonstrated that SIM0235 has a significant anti-tumor efficacy and synergistic effects when combined with PD-L1 antibodies.
Furthermore, safety evaluation results including the GLP repeated dosing toxicity study have shown that SIM0235 is safe. Throughout all such studies, no effects on the central nervous system, respiratory system and cardiovascular system have been observed.