Shanghai, China and Philadelphia, U.S. — April 13, 2020 — Antengene announced today that it has dosed the first patient in Taiwan, China in its phase 1 open-label clinical trial of ATG-019 (KPT-9274), a dual inhibitor of both PAK4 and NAMPT. This trial is being conducted to evaluate the safety and tolerability of ATG-019 monotherapy or ATG-019 combined with niacin ER (vitamin B3/nicotinic acid), for the treatment of advanced solid tumors or non-Hodgkin’s lymphoma.
ATG-019 is a first-in-class, also the only orally bioavailable dual-target inhibitor targeting both p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT). PAK4 regulates numerous fundamental cellular processes, including intracellular transport, cellular division, cell shape and motility, immune defense and the development of cancer. PAK4 interacts with many key signaling molecules involved in cancer development such as beta-catenin, CDC42, Raf-1, BAD and myosin light chain. The overexpression and overactivation of PAK4 lead to tumor proliferation and metastasis and show a negative correlation with the infiltration of immune cells, leading to tumor proliferation and metastasis. NAMPT is the rate-limiting enzyme in the metabolic scavenging pathway that utilizes nicotinamide to replenish nicotinamide adenine dinucleotide (NAD), an essential metabolic cofactor and second messenger. Inhibition of NAMPT can effectively inhibit the energy metabolism and growth of tumor cells.
In May 2018, Antengene entered into a broad strategic collaboration with Karyopharm Therapeutics Inc. (Nasdaq: KPTI) and obtained exclusive rights for development and commercialization of four clinical stage, novel, oral drug candidates, including KPT-9274 (ATG-019), in various Asian countries and regions. As an oral small molecule inhibitor with the novel mechanism with novel targets, ATG-019 inhibits the occurrence, development, invasion and migration of tumors through the precise targeting and inhibiting both PAK4 and NAMPT. Preclinical studies has demonstrated the significant inhibitory effect of ATG-019 on multiple tumors types including lung cancer, multiple myeloma, leukemia, and lymphoma, etc.
“We are pleased that the first patient of ATG-019 was successfully enrolled and dosed. This is our first step in developing PAK4/NAMPT dual-target inhibitor,” said Dr. Jay Mei, founder, chairman and CEO of Antengene,” In addition to conducting the clinical trial for the treatment of advanced solid tumors and non-Hodgkin’s lymphoma, Antengene is also exploring the potential for ATG-019 in the treatment of different indications and in combination with existing regimens based on the anti-proliferative activity of ATG-019 on cancer cells. We hope to explore its potential from multiple dimensions in the near future. “
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.