News: Anti-fibrotic LOX family inhibitor program to progress to Phase Ib trial

Thomas R. Cox, Oct 2019

Following a successful Phase Ia trial of their oral anti-fibrotic systemic LOX inhibitor, Pharmaxis are now moving into a Phase Ib multiple ascending dose (MAD) study in healthy volunteers.

This is an exciting time for the Matrix and Metastasis team as we have been collaborating closely with Pharmaxis recently in developing a pre-clinical portfolio to help build a case for potentially transitioning this compound through to a clinical trial in pancreatic cancer patients. Pharmaxis is already seeking to progress this compound in the myelofibrosis space, and so working with our team, we are exploring the potential for this exciting anti-fibrotic compound in other cancer settings.

Pharmaxis Systemic LOX inhibitor

This is the second part of the Phase I trial that Pharmaxis is undertaking to evaluate the safety of their drug in humans. The successful completion of the Phase Ia element showed that a single dose of the drug was well tolerated with no safety concerns, Importantly, the data collected also showed great phamacokinetics and a clear dose-related inhibition of the LOX family of enzymes, their primary target.

Dose dependent reduction in LOX plasma activity

The LOX family of enzymes are fundamental to our bodies ability to produce collagen, the major component of tissue fibrosis and scar tissue. Many solid tumours, including pancreatic cancers produce large amounts of fibrosis (scar like tissue) in and around the tumour which is known to reduce the efficacy our frontline chemotherapies. By blocking this fibrosis we are hoping to boost the effectiveness of the chemotherapy we already give to pancreatic cancer patients.

The next element is a Phase Ib, which is a double-blind placebo-controlled study in 16 patients, divided into two groups with each group receiving a different dose or placebo daily for 14 days.

The drug is an oral once-a‐day drug that inhibits all lysyl oxidase family members (LOX, LOXL1, 2, 3 & 4). The compound successfully cleared pre‐clinical safety and 3‐month toxicity studies and has shown significant reductions in fibrosis in in-vivo models of kidney, lung and liver fibrosis as well as myelofibrosis and with our help, pancreatic cancer.

Successful completion of the Phase Ib will be critical to Pharmaxis’ program working towards delivering novel stromal targeting (anti-fibrotic) agents into the clinic for myelofibrosis patients, and will also support our collaboration investigating how we might also be able to transition this compound into the clinic for pancreatic cancer patients.

About Pharmaxis

Pharmaxis (ACN082811630) is an Australian pharmaceutical research company focused on inflammation and fibrosis with a portfolio of products at various stages of development and approval. The company’s development pipeline is centred on its expertise in amine oxidase chemistry and includes Lysyl Oxidase Like 2 (LOXL2) inhibitors under clinical development for fibrotic diseases of the heart, kidney, liver and lung, and Lysyl Oxidase (LOX) inhibitors under clinical development for severe fibrotic diseases including pancreatic cancer and myelofibrosis. For more information about Pharmaxis, please see