Bayer Submits IND Application in China for BAY 2965501, a Novel DGKζ Inhibitor for Cancer Immunotherapy

▎Edited by the WuXi AppTec content team

Today (February 6), the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced,Bayer has filedThe clinical trial application for BAY 2965501 tablets has been submitted and accepted. Public information indicates that this is a novel cancer immunotherapy.For aDGKζ Inhibitor。

Screenshot source:CDE Official Website

Public data shows that DGKζ, a member of the diacylglycerol kinase family, plays a crucial regulatory role in multiple cell signaling pathways. Studies have found that the expression level of DGKζ is increased in various tumors and is associated with tumorigenesis, progression, and prognosis; thus, DGKζ is considered a new target for cancer immunotherapy.

According to literature reports, DGKζ inhibitors block the activity of DGKζ, thereby preventing the proliferation and survival of tumor cells.Specifically, DGKζ can catalyze on biological membranesDiacylglycerol（DAG）Converted to phosphatidic acidDown-regulation of T cell activation,Thereby serving as a ligand-independent intracellular immune checkpoint. InhibitionDGKζHas been provenCan enhance the initiation of T cells to suboptimal tumor antigens,And overcome multiple immunosuppressive mechanisms in the tumor microenvironment in a TCR-dependent manner.

According to publicly available information from Bayer, BAY 2965501 was co-developed by Bayer AG and the German Cancer Research Center (DKFZ) as aHighly Selective Oral DGKζ Inhibitor。In preclinical studies,This compound can increase natural killer cell and T-cell mediated tumor cell killing, and enhance interleukin-2-induced natural killer cell activation., and can overcome the inhibitory signals of transforming growth factor β, prostaglandin E2, and adenosine signaling in T cells. In vitro studies also indicate,Compared with anti-PD-1 antibody monotherapy, BAY 2965501 combined with anti-PD-1 antibodyCan reduce tumor growth ratePreclinical toxicology studies showed that the product had only low-grade gastrointestinal effects, indicating clinical tolerability.This preclinical study data was previously published in 2023.American Association for Cancer Research (AACR) Annual MeetingPublished on.

According toClinicalTrialsAccording to the official website, Bayer has just initiated the first Phase 1 clinical study of BAY 2965501 in humans in early 2024 in the United States, Japan, and other regions. This study aims to evaluate the safety, tolerability, and preliminary efficacy of the drug as a monotherapy or in combination with an anti-PD-1 monoclonal antibody for the treatment of advanced solid tumors. The focus of this research is on certain types of skin cancer, kidney cancer, stomach cancer, and lung cancer.