LAT1 has been shown to be specifically expressed on cancer cells and activated immune cells, contributing to the proliferation of cancer cells and the activation of immune cells in autoimmune diseases, indicating that our LAT1 inhibitors have the potential to be an emerging treatment for cancer and autoimmune diseases.

LAT1 has attracted interest from researchers around the world, and related papers have proliferated in recent years. Based on the LAT1 gene patent held by the founder until 2019, we have been the first in the world to develop LAT1 inhibitors, demonstrating their efficacy and safety in humans. Our LAT1 inhibitors have been internationally acclaimed, including multiple oral presentations at the American Society of Clinical Oncology (ASCO) and approaches from researchers around the world for co-development.

LAT1 belongs to the SLC transporter superfamily and plays an important role in transporting large neutral amino acids that are essential for the growth and proliferation of cancer cells.

When cells become cancerous and begin to multiply rapidly, the expression of LATl on the cell membrane is increased, and the uptake of amino acids increases, leading to explosive cell growth. In fact, LATl has been confirmed to be overexpressed in many solid cancers, including biliary tract cancer, pancreatic cancer, and brain tumors, and is known to be closely related to lymph node metastasis, cell proliferation, angiogenesis, and even shortened patient survival.

In addition, it has been suggested that LATl may influence the immune cells surrounding cancer cells by taking up amino acids, indirectly promoting tumor growth through immune evasion. This is due to the following reasons: Amino acids are essential for T cell activation, differentiation, and even functioning, playing a crucial role not only as a source of energy but also as a substrate for the biosynthesis of proteins and nucleic acids. In the tumor microenvironment, tumor cells compete with T cells for amino acids by expressing LATl highly, resulting in the depletion of extracellular amino acids. As a result, T cells cannot maintain their original antitumor function, resulting in impaired proliferation and survival, and reduced effector function. In this way, the preferential use of amino acids by cancer cells through LAT1 leads to immune cell exhaustion, which in turn promotes cancer cell growth and immune evasion. Therefore, in addition to the direct effect of limiting the uptake of amino acids by cancer cells and preventing their growth, it is also suggested that LATl inhibitors may restore the antitumor function of immune cells around cancer cells.

Against this background, LATl inhibitors that inhibit LATl function are extremely promising as new therapeutic agents for solid tumors, and their efficacy has been demonstrated at the cellular level and in animal models by researchers around the world (e.g., Cancer Sci., 2016, 107,1499-1505; Cancer Sci., 2009, 101, 173-179; Scientific Reports, 2023, 13, Article number 13943) o In addition, we have confirmed the efficacy of LATl inhibitors against biliary tract and colorectal cancers in humans in Phase 1 and Phase 2 clinical trials conducted in Japan, and have demonstrated clinical potential.

Many previous research results have also shown that LATl can be a new therapeutic target for autoimmune diseases. LATl is responsible for regulating the mTOR pathway and helping immune cells proliferate and release substances that cause inflammation (inflammatory cytokines). Therefore, it has been shown that inhibition of LATl function by genetic methods or LAT1 inhibitors reduces the release of inflammatory cytokines from overactivated immune cells (e.g., Chem Biol., 2006, 13,1153-1160; J Allergy Clin lmmunol., 2020, 145, 199- 214.ell) o

Based on this finding, LATl inhibitor inhibition of LATl function has the potential to be a new therapeutic approach for autoimmune diseases in which the immune system overreacts. In particular, in autoimmune diseases such as multiple sclerosis, which cause inflammation of the nerves, inhibiting LATl is expected to prevent damage to nerve cells caused by inflammation and oxidative stress, and LATl inhibitors are suggested to be a promising therapeutic strategy for neuroinflammatory diseases such as multiple sclerosis.