Date: 2014-07-09
Type of information: Results
phase: preclinical
Announcement: results
Company: Domainex (UK)
Product: selective inhibitors of IKK-epsilon and TBK1
Action mechanism:
Disease: chronic obstructive pulmonary disease (COPD) inflammatory diseases
Therapeutic area: Inflammatory diseases - Respiratory diseases
Country:
Trial details:
Latest
news: * On July 9, 2014, Domainex, a UK-based drug discovery company developing first-in-class small-molecule inhibitors of two closely-related pro-inflammatory kinases - TBK1 and IKK-epsilon (IKKε), announced that its lead compound has demonstrated a more potent effect in a key model of chronic obstructive pulmonary disease than either the PDE4 inhibitor roflumulast or a p38 inhibitor currently in late-stage clinical development. In the present study, Domainex compared the effect of oral doses of its compound with the same oral doses of either roflumilast or a p38 inhibitor in this COPD model. The Domainex compound showed more than twice the effect of the comparator drugs in reducing the cigarette smoke-induced influx of inflammatory cells, particularly neutrophils, into the lung. Domainex has previously shown that its inhibitors of TBK1 and IKKε are potent anti-inflammatory agents, which can inhibit signaling pathways activated by Toll-like Receptors and IL-17. This data suggests that these compounds may have utility in COPD and other inflammatory diseases including rheumatoid arthritis, lupus and psoriasis. The company has been awarded £1.4m by the Technology Strategy Board via the Biomedical Catalys and these funds will enable Domainex to progress the COPD programme to IND. * On April 7, 2014, Domainex has announced that it has successfully completed a series of laboratory studies examining the in vivo effects of its proprietary selective inhibitors of IKK-epsilon and TBK1 in inflammation models. In four separate studies a lipopolysaccharide (LPS) challenge was delivered either to the lungs or systemically to mimic the effect of inflammatory disease. In these experiments Domainex showed that its orally-delivered compounds can inhibit the expression of a number of pro-inflammatory cytokines including TNF-alpha, RANTES, IL-1-beta, and IL-6, and maintain prolonged activity against many of the cytokines for at least 20 hours. No side-effects were evident in these studies. These results are extremely promising in the search for new treatments of life-limiting diseases such as chronic obstructive pulmonary disease (COPD).Domainex will continue to study the utility of these compounds as treatments for COPD, and other inflammatory diseases. It hopes to partner the programme soon and to proceed to Phase I Clinical Trials.
