News: Anti-fibrotic LOX family inhibitor program to commence Phase I trials

Thomas R Cox, Nov 2018

We’re exited to reveal that we have been working hard with Pharmaxis on the development of their lysyl oxidase (LOX) systemic inhibitor for the potential use as a stromal co-targeting agent in pancreatic cancer.

Pharmaxis has developed an oral drug that inhibits all LOX family members, and which has shown to lead to significant reductions in fibrosis (scarring) in in-vivo models of kidney fibrosis, lung fibrosis, myelofibrosis and now with our help, in models of pancreatic cancer.

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.

We are now collaboroating with Pharmaxis to further investigate the therapeutic potential of their systemic LOX family inhibitor in our models of pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer.

Watch a presentation on Fibrosis, LOX and Cancer by Dr Thomas R. Cox, Leader of the Matrix and Metastasis Team here.

A Phase I clinical trial in healthy volunteers evaluating safety is due to commence in February 2019. This double-blind placebo controlled study will consist of two stages. The first single ascending dose (SAD) stage will be conducted in 40 healthy subjects divided into five groups with each taking a different single dose or placebo. The second multiple ascending dose stage will be conducted in 16 healthy subjects divided into two groups with each group receiving a different dose or placebo for 7 days.

The aim of the Phase I trial is to determine whether the drug is safe to move forward to the next stage to check for efficacy. Successful completion of this Phase Ia will be critical to Pharmaxis’ program working towards delivering novel stromal targeting (anti-fibrotic) agents into the clinic for myelofibrosis patients, and will support us in our collaboration with them evaluating the potential of this compound as a stromal co-targeting agent in pancreatic cancer.

PXS LOX Systemic Inhibitor

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 www.pharmaxis.com.au.