Synairgen recently reported positive data from its ongoing work in partnership with Pharmaxis to develop a lysyl oxidase type 2 enzyme (LOXL2) inhibitor as a new treatment for idiopathic pulmonary fibrosis (IPF).
Synairgen is now conducting toxicology studies and plans to initiate a Phase 1 clinical trial this year.
IPF is a fatal condition of unknown cause in which the lungs become scarred and breathing becomes increasingly difficult. In patients with IPF a build-up of scar tissue (formed largely of collagen) in the lungs damages its structure affecting normal uptake of oxygen into the blood.
LOXL2 is a member of a family of enzymes that stiffens scar tissue through the formation of cross-links between collagen molecules.
The company previously reported that LOXL2 inhibitors reduced the cross-linking of collagen fibers in an in vitro model of IPF. In addition, researchers found that the collagen fibers were less organized when in the presence of such inhibitors, ultimately resulting in a reduction in tissue stiffness of around 50 percent in the lungs, which can positively alter disease progression.
Now, Synairgen reported that oral administration of one of these LOXL2 inhibitors in a preclinical model of lung fibrosis significantly inhibited cross-link formation, reduced fibrosis score, and improved lung function.
“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, Synairgen’s CEO, said in a press release.
Synairgen and Pharmaxis are jointly working to develop small LOXL2 inhibitors for the treatment not only of IPF, but also of other fibrotic conditions, such as kidney fibrosis, cardiac fibrosis, and non-alcoholic steatohepatitis (NASH).
Marsden said 2017 will be an important year for Synairgen.
“Subject to the successful completion of ongoing pre-clinical work, we expect to commence Phase 1 clinical trials of the LOXL2 inhibitor during the second half of 2017,” he said. “The window for licensing the LOXL2 program to a pharmaceutical partner will open at the end of Phase 1.”
IPF is estimated to affect up to 132,000 people in the U.S., and approximately 50,000 new cases are diagnosed every year. The clinical symptoms of the disease are nonspecific and can be shared with other pulmonary and cardiac diseases.