TEW-7197 is originally developed in Ewha Womans University with government support of Program for Disease-Based Discovery of Global New Drug Candidates and out-licensed from Ewha to MedPacto. MedPacto made a co-development partnership with OncoVeture, an independent foundation whose funding comes from Korean Government in Sept. 2013.
TEW-7197 is a reversible inhibitor of protein serine/threonine kinase activity of transforming growth factor (TGF)-β receptor type 1 (TGFBR1, ALK5). It inhibits the phosphorylation of TGF-β R Smads (Smad2 and Smad3) and the nuclear translocation of its heteromeric complex with Smad4 in the TGF-β receptor-mediated signaling pathway. TEW-7197 showed antitumor activity in various mouse models of breast cancer, melanoma, hepatocellular carcinoma (HCC), and glioblastoma. In normal tissue homeostasis, TGF-β has been shown to be a potent growth inhibitor for epithelial, hematopoietic, and immune cells. In cancer progression, TGF-β changes its roles as the disease progresses.
During the early stages of tumorigenesis, TGF-β has preventative or tumor-suppressing activity. However, as tumor development progresses to later stages, TGF-β promotes epithelial to mesenchymal transition (EMT), prevents immune surveillance, and facilitates tumor cell proliferation. The role of TGF-β in EMT and tumor proliferation provides a tool for inhibiting cancer progression by blocking the TGF-β signaling pathway. TEW-7197 showed an excellent profile as a cancer drug and should be a candidate to free patients from various cancers. MedPacto has a plan to start a clinical phase 1 program in April 2014.