Synairgen announced it successfully completed three-month toxicity studies on LOXL2 (lysyl oxidase like 2) inhibitor candidates for treating idiopathic pulmonary fibrosis (IPF). The LOXL2 program, developed in collaboration with Pharmaxis, may move into Phase 2 trials.
Synairgen and Pharmaxis began their collaboration in 2015 to develop the oral LOXL2 inhibitors PXS-5382A and PXS-5338K to lessen fibrosis (scar tissue) in IPF. Earlier tests showed reduced fibrosis in IPF mouse models treated with the inhibitors.
LOXL2 is part of the family of lysyl oxidase proteins that are secreted by cells into the extracellular matrix to offer biochemical support to tissues and organs. Previous examinations of lung tissues from IPF patients showed that LOXL2 plays a critical role in the development of lung tissue scarring, leading to IPF.
Pharmaxis-led clinical trials in Australia, ACTRN12617001564347 and ACTRN12617001444370, tested the safety, pharmacokinetics (the medicine’s absorption, distribution, metabolism, and excretion from the body), and pharmacodynamics (the mechanism of action) of the two LOXL2 inhibitors in IPF and non‐alcoholic steatohepatitis (NASH, a serious condition characterized by liver inflammation and scarring).
In each trial, 48 healthy participants received either a placebo or a single ascending dose of the inhibitor, followed by multiple ascending dose assessments in 24 other healthy participants, receiving placebo or an inhibitor.
Results showed that both inhibitors, PXS-5382A and PXS-5338K, were stable when administered. The trials also confirmed the success of one daily dose, and that it effectively inhibited LOXL2, supporting previous preclinical study results.
With completion of these trials, Pharmaxis can now begin pursuing commercial partnerships.
“The successful completion of the longer-term toxicology studies completes the data set,” Richard Marsden, CEO of Synairgen, said in a press release. “Pharmaxis is now conducting a final series of scientific briefings to potential partners.”
The two companies revised their collaboration agreement in 2017, with Pharmaxis taking full responsibility for the LOXL2 clinical program, and Synairgen receiving a $6.45 million upfront payment, and around 17% of any future net partnering proceeds from all potential fibrotic treatments for the inhibitors.
Under the agreement, Synairgen holds no financial responsibilities for further development of LOXL2 candidates, but will lend technical support during the licensing process.