Bayer Submits IND Application in China for BAY 2416964, a First-in-Class Oral AhR Inhibitor for Cancer Immunotherapy

Source:Pharma Perspective

According to the latest public announcement by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration, Bayer has submitted a clinical trial application for its Class 1 new drug, BAY 2416964 tablets, which was accepted by the CDE on October 16. BAY 2416964 is a highly selective aryl hydrocarbon receptor (AhR) inhibitor. Given that AhR is highly expressed in various tumors and plays an immunomodulatory role, AhR-targeting modulators are considered a novel class of immunotherapies. Currently, BAY 2416964 is still in the early stages of global development, and this marks Bayer’s first submission of a clinical trial application for this investigational drug in China.

Source: CDE Official Website

The aryl hydrocarbon receptor (AhR) is a protein found in immune cells that modulates immune responses by integrating various signals, such as those from the human microbiota and amino acid metabolism. Early studies have revealed that AhR plays a pivotal role in regulating immunosuppression within the tumor microenvironment, with high expression of AhR observed in various cancers, including lung cancer, colorectal cancer, and head and neck squamous cell carcinoma. Additional research has demonstrated that AhR inhibitors exhibit potent anti-proliferative activity in specific cell types with high AhR expression, promote apoptosis, and inhibit Erk phosphorylation. Consequently, AhR is considered a promising target for developing therapies against tumors with high AhR expression, and it holds potential for combination therapy with other drug classes to enhance treatment efficacy.

Public information indicates that BAY 2416964, an oral AhR inhibitor developed by Bayer, can block CYP1A1 transcription mediated by different AhR agonistic ligands, directly interact with AhR, and inhibit ligand-induced translocation of AhR to the nucleus.

In April 2020, during the “New Drugs on the Horizon” session of the American Association for Cancer Research (AACR) Annual Meeting held online, Bayer presented preclinical study results for BAY 2416964. The study demonstrated that it is a potent, selective, and cross-reactive AhR modulator capable of exerting diverse antitumor immunomodulatory effects.

Based on publicly available information, BAY 2416964 demonstrates inhibitory effects on specific tumor models at various doses and dosing frequencies. In vitro studies have shown that BAY 2416964 can modulate the activity of murine T cells and myeloid-derived suppressor cells. Further research has revealed that it induces pro-inflammatory effects across different human immune cell subsets, and its combination with anti-PD-1 monoclonal antibodies further enhances T-cell activity in mixed lymphocyte reactions (MLR). In specific animal model experiments, oral administration at a dose of 30 mg/kg once daily resulted in observed inhibition of tumor growth, whereas no therapeutic effect was observed in immunodeficient mice. Additional studies have demonstrated that BAY 2416964 can modulate the immune composition of the tumor microenvironment in specific models. Furthermore, both in vitro and in vivo experiments have indicated a favorable safety profile for this compound.

Globally, Bayer’s research and development of BAY 2416964 has entered Phase I clinical trials. A search of the ClinicalTrials.gov website reveals that a clinical trial is currently recruiting patients at multiple clinical research centers in the United States. This study is a first-in-human dose-escalation investigation of the AhR inhibitor BAY 2416964 in patients with advanced cancer.

Image source: ClinicalTrials.gov website

In China, according to public information from the Center for Drug Evaluation (CDE) and the Chinese Clinical Trial Registry and Information Publicity Platform, BAY 2416964 had not previously undergone clinical studies in China. This marks Bayer’s first submission of a clinical trial application in China, which has been accepted by the CDE.

Congratulations on the acceptance of the clinical trial application for Bayer’s novel cancer immunotherapy. We hope this investigational new drug will soon receive clinical trial approval in China, and we look forward to its rapid breakthroughs and progress globally, bringing new treatment options to patients.

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