Core Technology
TaiwanJ’s proprietary technology is based on the discovery of a series of small molecules that antagonize TLR 4 signaling for potential therapeutic application of inflammation-associated organ damage resulting from TLR4-stimulated inflammatory cascade.   
Mammalian TLRs include intracellular and extracellular receptors that recognize microbial proteins, nucleic acids, carbohydrates, and lipids to activate host defense mechanisms against invading pathogens that produce such molecules. TLR4 for example is a cell surface protein, and present in macrophages such as the Kupffer cells of the liver. TLR4 plays an important role in recognizing and mediating macrophage activation and pro-inflammatory cytokine release along the immunological cascade.  Activation of pro-inflammatory cytokines, including tumor necrosis factor (TNFa) is pivotal in the progression of liver injury. 
TLR4 recognizes bacterial lipopolysaccharides (LPS), major constituents of the outer membrane of infectious Gram-negative bacteria. Activation of TLR4 signaling by endotoxins such as LPS triggers many pathophysiological events, resulting in the release of a myriad of pro-inflammatory cytokines and mediators that result in hepatic injury. This pathological process begins with inflammation and often progresses to fibrosis, cirrhosis, liver failure and cancer. The importance of TLR4 signaling in liver disease and other diseases such as Crohn’s disease/ulcerative colitis, diabetes, and various cancers has been demonstrated and reviewed in recent years.
On the other hand, TLR4 recognizes endogenous ligands released from damaged or dying cells. Activation of a TLR by its relevant ligand rapidly ignites a complex intracellular signaling cascade that ultimately results in upregulation of inflammatory genes and production of pro-inflammatory cytokines, interferons and recruitment of myeloid cells. TLR4 is most abundant in antigen-presenting cells, and upon activation stimulates expression of co-stimulatory molecules required to induce an adaptive immune response. Whilst a robust TLR response is critical for survival and defense against invading pathogens, inappropriate signaling in response to alterations in the local microflora environment can be detrimental. Such ‘unhelpful TLR responses’ could form the basis for a large number of gastrointestinal and liver disorders, including inflammatory bowel disease, viral hepatitis, autoimmune liver diseases and hepatic fibrosis (TestroAG andKumar Visvanathan, 2009). 
Proof of concept studies of TLR4 antagonists in Crohn’s disease and chronic liver disease in alcoholic patients have been reported by Smith et al. (2013) and Yen et al. (2006) respectively.

Autotaxin (ATX) inhibitors
ATX is a secreted enzyme that catalyzes the hydrolysis of lysophosphatidyl choline (LPC) to generate lysophosphatidic acid (LPA). LPA, a derivative of phospholipids, acts as a potent mitogen due to its activation of LPAR1-LPAR6. Because of its ability to stimulate cell proliferation, aberrant LPA-signaling has been linked to cancer. Dysregulation of autotaxin or the LPA receptors can lead to hyperproliferation, which may contribute to oncogenesis and metastasis. In addition, LPA may be the cause of pruritus in individuals with cholestatic diseases. Consequently, the ATX-LPA signaling axis has been implicated in cancer metastasis, fibrotic diseases and inflammation among other diseases. ATX levels are elevated in the serum of liver fibrosis patients in proportion to severity of fibrosis. ATX inhibitors (ATXi) have been pursued as a novel therapy for idiopathic pulmonary fibrosis (IPF), a fatal disease, with encouraging results. On the other hand, TaiwanJ is currently focused on the use of ATXi in the treatment of chronic liver diseases (NASH and NAFLD). Potent leads have been identified, pending proof of concept study in in vivo efficacy models of NASH. The platform may be extended to cover renal fibrosis associated with diabetic nephropathy and IPF.

Inhibitors of IL-4 and IL-13
Lines of preclinical evidence strongly support a role for both IL-4 and IL-13 in the development and maintenance of allergic inflammation in the lung and skin. Concurrent inhibition of IL-4 and IL-13 can block IgE responses primarily driven by IL-4, and block mast cell activation, lung inflammation, airway hyperresponsiveness (AHR), lung eosinophilia, and mucin gene expression responses primarily driven by IL-13. This can be accomplished by selective suppression of Th2-biased pathway with small molecules that work through interfering Th2-specific transcriptional factors, or interactions between antigen presenting cells and macrophages and other cell types in the airway. Alternatively, novel inhibitors may have direct effect on macrophages, mast cells, neutrophils, etc.