Pharmaxis Ltd and Synairgen plc recently announced a collaboration with the goal of developing a selective inhibitor to the lysyl oxidase type 2 enzyme (LOXL2) as a therapy for idiopathic pulmonary fibrosis (IPF).
IPF is a progressive fatal lung disease in which the alveoli and the lung tissue are damaged, becoming thick and scarred (fibrosis), leading to severe breathing difficulties and compromising oxygen transfer between the lungs and the bloodstream. The disorder is characterized by a shortness of breath that gradually worsens, with respiratory failure being the main cause of death. IPF has a poor prognosis and around two-thirds of the patients die within five years after being diagnosed. It has no cure and it is estimated that almost 130,000 individuals in the United States and 5 million worldwide suffer from the disease.
The LOXL2 is considered a therapeutic target for IPF because this enzyme promotes the generation of the scar tissue that irreversibly damages the lungs in IPF patients. Inhibiting LOXL2 is expected to slow the formation of scar tissue and improve the patient’s survival rate.
Under the terms of the collaboration, Synairgen will fund the LOXL2 inhibitor program from Pharmaxis, having access to its BioBank and lung models, and collaborating with the IPF research team at the University of Southampton in the United Kingdom in order to conduct pre-clinical and early clinical trials. The companies expect to develop the IPF program up to phase 1 or phase 2a clinical trials, at which time they will search for a license partner.
Apart from this collaboration, Pharmaxis plans to continue developing compounds for other conditions where LOXL2 inhibitors may have potential therapeutic action like liver and kidney fibrosis, and also metastatic cancer. Under the terms of the agreement, the license of the LOXL2 program can, however, be extended to multiple indications.
“We have continued to make good progress in our preclinical LOX inhibitor program and in particular on LOXL2 small molecule inhibitors to treat various diseases where fibrosis is a major problem. The significant interest among leading clinicians and pharmaceutical companies in the role of LOXL2 in a number of different diseases has highlighted the need for us to collaborate for selected indications in order to fully exploit the potential value of our intellectual property,” explained the Pharmaxis CEO Mr. Gary Phillips in a press release. “Synairgen has a demonstrated excellence in respiratory drug development, having successfully licensed its inhaled IFN-beta Phase 2 program to AstraZeneca. We believe our collaboration with Synairgen will accelerate the development of a highly competitive once-a-day oral treatment for patients with IPF and enable Pharmaxis to develop LOXL2 inhibitors for other potential indications such as liver and kidney fibrosis, and cancer.”
“We are delighted to be collaborating with Pharmaxis in idiopathic pulmonary fibrosis, a severe and fatal lung disease. Pharmaxis has a proven competence in the discovery and development of novel molecules, making it an ideal partner. LOXL2 is a target which is of interest not only to our IPF clinical experts in Southampton but also to large pharmaceutical companies; in 2011 Gilead Sciences acquired Arresto Biosciences for $225 million for its Phase I LOXL2 targeting antibody simtuzumab and is currently conducting a large efficacy trial in IPF,” said Synairgen CEO Mr. Richard Marsden. “Using existing financial resources from our fundraising in 2014, we will apply our BioBank platform of advanced human tissue models and understanding of respiratory biology to develop the LOXL2 inhibitor. We look forward to working closely with Pharmaxis and the world class academics at the University of Southampton to progress this opportunity into the clinic in patients with IPF.”