On April 13, 2020 Antengene reported 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 (Press release, Antengene, APR 13, 2020, View Source [SID1234556300]). 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.
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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. "