Press Release

Mar 12, 2020

Phase 2 clinical trial of ATG-008 as targeted therapy for advanced non-small-cell lung cancer initiated in China

Shanghai, China and Philadelphia, U.S. -- March 12, 2020 -- Antengene announced the launch of a clinical trial of ATG-008 for the treatment in advanced Chinese non-small-cell lung cancer (NSCLC) with nuclear factor erythroid 2-like 2 (NFE2L2) mutation. This trial is an open-label, multi-center, umbrella phase 2 clinical trial which was initiated by Professor Yilong Wu, the principal investigator, from Guangdong Provincial People's Hospital.This trail aims to evaluate the efficacy of ATG-008 for advanced NSCLC patients with NFE2L2 mutation.

According to the data released by the National Cancer Center in 2019, lung cancer tops China's malignant tumor incidence rate. Of all lung cancers, NSCLC accounts for about 85%. With no obvious symptoms in the early stage, most patients are already in the advanced stage when they found themselves with NSCLC, leading to limited effects of surgery and radiotherapy as local therapy. Therefore, the exploration of targeted therapies has great significance for advanced NSCLC patients in clinical trials.

ATG-008 is a TORC1/TORC2 kinase dual-targeted inhibitor that acts on the mTOR pathway. It regulates cell growth and metabolism by controlling the binding of mTOR with other proteins, thus inducing tumor cell apoptosis and inhibiting its proliferation. Previous studies have shown that ATG-008 has favorable effect in the treatment of patients with advanced liver cancer, and phase 2 clinical trials of ATG-008 for the treatment of advanced liver cancer are being conducted in Mainland China, Taiwan and South Korea. Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor related to oxidative stress and is encoded by NFE2L2 gene. NFE2L2 mutation lead to nuclear transport of Nrf2 and upregulate the activity of mTOR pathway. Pre-studies have confirmed tumor formation induced by NFE2L2 mutation through activation of the mTOR pathway and preliminary effectiveness of mTOR inhibitors on NFE2L2 mutation tumors, and a considerable proportion of NFE2L2 mutation exist in advanced NSCLC. Therefore, the effectiveness of ATG-008 on advanced NSCLC patients with NFE2L2 mutation is worth looking forward to.

"The development of precision medicine has moved forward the treatment of NSCLC from cytotoxic therapy to targeted therapy with higher tolerability and efficacy. As a small-molecule drug for targeted therapies, ATG-008 can accurately inhibit cancer cells, enhance the safety of the treatment process and improve the prognosis of patients." said Dr. Jay Mei, founder, chairman and CEO of Antengene, "we look forward to positive feedback from the trial and hope that lung cancer patients in China can share the benefits from it as soon as possible."

About ATG-008

ATG-008 is a new generation of dual target inhibitors of mTOR kinase, which is currently in Phase 2 clinical trial and has not been marketed in any country or region. mTOR is in the key position of tumor signaling pathway, and mTOR inhibitors are widely used in tumor targeted therapy.2017 Albert Lasker Basic Medical Research Award was granted to Michael N. Hall, who discovered the nutrient-activated TOR proteins and their central role in the metabolic control of cell growth.

About Antengene

Antengene is a China-and-U.S. based biopharmaceutical company focusing on drug discovery, clinical development and the commercialization of innovative therapeutics to meet unmet medical needs. Antengene aims to provide the most advanced and first-in-class anti-cancer drugs and other treatments for patients in China, Asia and around the world. In April 2017, Celgene (now officially acquired by Bristol-Myers Squibb, and become the world’s top ten pharmaceutical company after the merge), a global leading innovative biopharmaceutical company became a long-term strategic partner and obtained an equity position in Antengene. In January 2020, former Celgene chairman and CEO Mark J. Alles joined Antengene Board of Directors and former Celgene China GM John Chin joined the company as Chief Business Officer.

At present, Antengene’s pipeline includes six clinical stage products:

ATG-010 (selinexor) is the first oral selective inhibitor of nuclear export compound with novel mechanisms in the world. In 2019, the U.S. FDA approved ATG-010 in combination with low-dose dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma. Currently, the registered clinical trials of ATG-010 in relapsed refractory multiple myeloma (RRMM) and diffuse large B-cell lymphoma (DLBCL) is ongoing in China. The compound is also in late clinical development for various other hematologic malignancies and solid tumors. In addition, preclinical studies have shown that inhibitors of nuclear protein export can effectively treat KRAS mutant tumor, and related clinical studies will be conducted within the year; ATG-008 is a second-generation dual mTORC1/2 inhibitor and is in a multi-regional clinical trial for treatment of advanced liver cancer, lung cancer, and several other tumors; ATG-016 is a second-generation oral selective inhibitor of nuclear export protein, and is currently being studied in myelodysplastic syndrome (MDS) as well as in several clinical trials of solid tumors, including colorectal cancer (CRC) and prostate cancer (PrC) ; ATG-019 is the first-in-class PAK4/NAMPT dual-target inhibitors, and is currently been studied in a number of clinical trials including non-Hodgkin's lymphoma (NHL), colorectal cancer, lung cancer, and melanoma. In addition, preclinical studies have demonstrated that ATG-019 in combination with anti-PD-1 antibodies can effectively improve the anti-tumor activity and is effective in patients who acquire resistance to anti-PD-1 therapy. Related clinical trial is about to initiate; ATG-527 is an innovative product under development for antiviral and treatment of autoimmune diseases, and has been in clinical trials conducted in Epstein-Barr virus (EBV), respiratory syncytial virus (RSV) infection, cytomegalovirus (CMV) infection and Systemic lupus erythematosus (SLE) and other related diseases; ATG-017 is a potent and selective small molecule extracellular signal–regulated kinases 1 and 2 (ERK1/2) inhibitor, in clinical development for the treatment of various solid tumors, non-Hodgkin's lymphoma, acute myelocytic leukemia (AML) and multiple myeloma. In addition, the drug discovery team of Antengene focuses on the early preclinical development of multiple innovative target drugs in the fields of small molecule, monoclonal and bi-specific antibodies. For more information, please visit www.antengene.com.