Synairgen Releases Data Showing Early Potential for LOXL2 Inhibitor to Treat IPF


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Synairgen released further positive data from its lysyl oxidase-like 2 enzyme (LOXL2) inhibitor program to treat idiopathic pulmonary fibrosis (IPF), being conducted in collaboration with Pharmaxis. A Phase 1 clinical trial is set to start this year, if toxicology studies are successfully completed.

Synairgen and Pharmaxis entered a collaboration in August 2015 to develop an oral LOXL2 inhibitor to reduce fibrosis in patients with IPF.

IPF results from the build-up of scar tissue that damages the structure of the lungs, affecting the uptake of oxygen into the blood. Scar tissue is formed largely by collagen, and LOXL2 is a member of a family of enzymes that stiffen scar tissue by forming cross-links between collagen molecules.

The company previously reported that these inhibitors can reduce cross-linking of collagen fibers in an in vitro, or lab cultured, model of IPF. This process resulted in a reduction in tissue stiffness of around 50 percent.

Now, in a preclinical model of lung fibrosis, the company demonstrated that the oral administration of one of these compounds also reduced fibrosis and improved lung function.

The reported data demonstrated that these enzyme inhibitors, by blocking LOXL2, reduced in a dose-dependent manner the cross-linking of collagen fibers, the company said in a press release. In addition, researchers found that the collagen fibers were less organized when in the presence of the inhibitors.

Inhibition of LOXL2, these results suggest, could improve lung function in patients with IPF.

“The effect of these inhibitors across different model types is very exciting, suggesting that inhibition of LOXL2 has the potential to improve lung function in severely ill patients with lung fibrosis by reducing tissue stiffness” Richard Marsden, chief executive officer of Synairgen, said in the release.

“2017 will be an important year for Synairgen. Subject to the successful completion of ongoing pre-clinical work, we expect to commence Phase I clinical trials of the LOXL2 inhibitor during the second half of 2017. The window for licensing the LOXL2 programme to a pharmaceutical partner will open at the end of Phase I,” he added.

Synairgen was founded by researchers at the University of Southampton and uses the university’s BioBank platform to discover and develop novel therapies for respiratory diseases.

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