Press Release

Apr 27, 2020

Antengene Doses First Patient with ATG-008, a mTOR1/2 Dual-targeted Inhibitor, for Advanced Solid Tumors and Hepatocellular Carcinoma of the Clinical Trial with Junshi Biosciences' Toripalimab

SHANGHAI, China and PHILADELPHIA, U.S.- April 27, 2020 - Antengene Corporation announced today that it has dosed the first patient with advanced solid tumors and hepatocellular carcinoma (HCC) in China in the clinical trial of its mTOR1/2 dual-targeted inhibitor ATG-008 combined with Toripalimab, an anti-PD-1 monoclonal antibody (trade name: Tuoyi) from Junshi Biosciences (1877.HK). In addition to ATG-008, Antengene is actively promoting clinical trials of several products in development combined with anti-PD-1 monoclonal antibodies for the treatment of multiple solid tumors and hematological tumors.

According to data released by the National Cancer Center in 2019, there are about 3.92 million new cancer cases and 2.33 million deaths in China in 2015. Among them, solid tumors such as lung, stomach, colorectal and liver cancers account for the top eight cancer incidence and mortality rates. The vast majority of patients with solid tumors are at mid- to late-stage, and in most cases, third line or subsequent treatment for advanced solid tumors has no standard treatment regimen. HCC is a common solid tumor, leading to the hundreds of thousands of deaths every year in China, about 85%-90% of which are hepatitis B virus positive (HBV+). With few symptoms in early-stage, patients will live on for only 3 to 6 months once diagnosed. Although new anti-tumor and hepatocellular carcinoma drugs have been approved in recent years, a large proportion of patients with advanced solid tumors and hepatocellular carcinoma still need safe and effective treatment regimens.

mTOR (mammalian target of rapamycin) is a serine/threonine protein kinase that promotes multiple tumor expression, playing an important role in the downstream of PI3K/AKT/mTOR signaling pathway, and it is dysregulated in approximately 80% of cancers. ATG-008 is a second-generation oral rapamycin-targeted protein (mTOR) kinase inhibitor that inhibits both TORC1 and TORC2, which ultimately leads to apoptosis and reduces proliferation of tumor cells. ATG-008 has been studied in clinical trials for multiple tumors including liver cancer, and has shown unique advantages in safety, tolerability and efficacy. Preclinical animal tests suggest that the combination of mTOR inhibitors with anti-PD-1 monoclonal antibodies has a synergistic antitumor effect on multiple tumor types.

According to Dr. Jay Mei, founder, chairman and CEO of Antengene: "China has a large number of solid tumor patients,with many tumor types like liver cancer having short average survival period and high mortality and recurrence rate. As a molecularly-targeted drug,ATG-008 has shown significant anti-solid tumor activity in previous trials and is expected to be a new pathway for the treatment of advanced solid tumors." He also pointed out that "We hope that with a combination therapy that focus on high prevalence tumor types in Chinese patients to further explore the potential of ATG-008 to bring innovative therapies to patients with liver cancer and advanced solid tumors in the Asia-Pacific region as early 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. Antengene is conducting several anti-tumor clinical trials of ATG-008 monotherapy and in combination with other drugs in the Asia-Pacific region.

As an innovative drug of Antengene approved to enter clinical trial in the Asian-Pacific region, ATG-008 is also the first drug in development of the same kind to enter clinical trial of advanced liver cancer. Six clinical studies of ATG-008 have been completed in the United States and Europe. At present, Antengene is conducting international multi-center clinical trial of ATG-008 for the treatment of advanced liver cancer in mainland China, Taiwan, and South Korea, and has obtained the support from “National Science & Technology Pillar Program during the Thirteenth Five-year Plan Period”. Available data indicate that ATG-008 has demonstrated encouraging anti-tumor signals in multiple tumor types including liver cancer.

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. On July 3, 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 and the stage of registered clinical trials for various other hematologic malignancies and solid tumors. In addition, preclinical studies have shown that inhibitors of nuclear protein export can effectively treat a wide range of tumors carrying KRAS mutation, and related clinical studies have been conducted recently; 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, including in combination with anti-PD-1 antibody; 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), gastric carcinoma (GC), triple-negative breast cancer (TNBC) 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.