Synairgen, the respiratory drug discovery and development company, today announces further positive data from its LOXL2 (lysyl oxidase-like 2 enzyme) inhibitor programme against the lung disease idiopathic pulmonary fibrosis (IPF), being conducted in collaboration with Pharmaxis (ASX: PXS). Successful completion of toxicology studies will enable commencement of Phase I clinical trials in H2 this year as planned.
Using cells from IPF patients, Synairgen has previously reported that these inhibitors can reduce cross-linking of collagen fibres in an in vitro model of IPF developed in collaboration with the University of Southampton and the Company has now demonstrated that this results in a reduction in tissue stiffness of around 50%. Today Synairgen also reports that oral administration of one of these compounds significantly inhibited cross-link formation, reduced fibrosis score and improved lung function (elastance) in a preclinical model of lung fibrosis (note 1). Together these results suggest that inhibition of LOXL2 using these novel inhibitors has the potential to improve lung function in patients with lung fibrosis by reducing tissue stiffness.
IPF is a fatal lung disease which, with a median survival of 2 to 3 years[1], carries a worse prognosis than many cancers. It affects up to 132,000 people in the US and approximately 50,000 new cases are diagnosed each year[2]. The current products for IPF have generated global revenues in excess of $1 billion in 2016[3]. Whilst the underlying cause of the disease is not fully understood, IPF results from the relentless build-up of scar tissue which, in turn, damages the structure of the lung affecting normal uptake of oxygen into the blood. The resultant stiffening of the lungs makes it increasingly difficult to breathe. Scar tissue is formed largely of collagen. LOXL2 is a member of a family of enzymes that stiffen scar tissue by forming cross-links between the collagen molecules.
Synairgen and Pharmaxis are collaborating to develop small molecule inhibitors of LOXL2 for the treatment of IPF and other fibrotic conditions including non-alcoholic steatohepatitis (NASH), kidney fibrosis and cardiac fibrosis.
Commenting on the results, Richard Marsden, CEO of Synairgen, said:“The effect of these inhibitors across different model typesisveryexciting,suggesting that inhibition of LOXL2 has the potential to improve lung function in severely ill patients with lung fibrosis by reducing tissue stiffness.
“2017 will be animportant year for Synairgen.Subject to thesuccessful completion of on-going pre-clinical work, weexpect to commence Phase I clinical trialsof the LOXL2 inhibitor during the second half of 2017. The window for licensing theLOXL2programme to a pharmaceutical partner will open at the end of Phase I.We also expect to hear the outcome of the AstraZeneca Phase II trial of interferon beta during the first half of 2017.“
Filed Under: Drug Discovery
