Oral pan-LOX Inhibitor (PXS-5505)

Oral pan-LOX Inhibitor - myelofibrosis and other cancers

Pharmaxis has developed an oral drug inhibiting all lysyl oxidase family members. The compound has shown significant reductions in fibrosis in in-vivo models of kidney fibrosis, lung fibrosis, myelofibrosis and pancreatic cancer. This all-encompassing LOX inhibitor is well positioned for the treatment of severe fibrosis as well as cancer with prominent stroma (connective tissue) or fibrotic metastatic niches. Pharmaxis plans to initially develop the compound for myelofibrosis.

Pharmaxis is also collaborating with a number of Australian and international clinical and academic groups with interest in LOX inhibition, including:

  • Myelodysplastic syndrome
  • Liver Cancer
    Rochester (NY)
  • Pancreatic Cancer
    Sydney (Garvan Institute of Medical Research), Rochester (NY)
  • Melanoma
  • Glioblastoma
    MD Anderson (Houston) and Charlie Teo Foundation
  • Head and Neck Cancer

A Phase 1 clinical trial in healthy volunteers commenced in February 2019 and reported in April 2020. The Phase 1 trial demonstrated a well-tolerated drug that effectively inhibits all enzymes in the lysyl oxidase family that are involved in fibrosis. Long term toxicity studies were completed clearing the way for 6-month phase 2 studies in several cancers with the opportunity to demonstrate disease modifying efficacy.

In mid 2020 the US Food and Drug Administration granted orphan-drug designation for the pan-LOX inhibitor PXS-5505 for the treatment of myelofibrosis. In August the FDA completed a safety review of the company’s Investigational New Drug (IND) application PXS-5505 and gave Pharmaxis permission to proceed with a phase 1c/2 clinical trial for the treatment of myelofibrosis in adults. Read the media release.

A Phase 1c/2a clinical trial in myelofibrosis patients commenced in February 2021. The study aims to demonstrate that PXS-5505 is safe and effective as a monotherapy in myelofibrosis patients who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs. The dose escalation phase of the study that is being conducted at sites in Australia and South Korea, aims to select the optimum dose of PXS-5505.  This first phase, that will recruit up to 18 patients, is expected to conclude and report in 2H 2021. It will be followed by a six-month dose expansion phase (24 patients) to evaluate safety and efficacy. Sites in other countries including the USA will be added for the dose expansion phase. Read the announcement Read the media release.

Access Pharmaxis Publications and Posters on LOX inhibitors



Primary myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material. Over time, this leads to progressive bone marrow failure. Under normal conditions, the bone marrow provides a fine network of fibres on which the stem cells can divide and grow. Specialised cells in the bone marrow known as fibroblasts make these fibres.

In primary myelofibrosis, chemicals released by high numbers of platelets and abnormal megakaryocytes (platelet forming cells) over-stimulate the fibroblasts. This results in the overgrowth of thick coarse fibres in the bone marrow, which gradually replace normal bone marrow tissue. Over time this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. This results in anaemia, low platelet counts and the production of blood cells in areas outside the bone marrow for example in the spleen and liver, which become enlarged as a result.

Primary myelofibrosis is a rare chronic disorder diagnosed in an estimated 1 per 100,000 population. It can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of primary myelofibrosis remains largely unknown. It can be classified as either JAK2 mutation positive (having the JAK2 mutation) or negative (not having the JAK2 mutation).

Source: Australian Leukemia Foundation: https://www.leukaemia.org.au/disease-information/myeloproliferative-disorders/types-of-mpn/primary-myelofibrosis/

Phase II
Description PXS5505-MF-101
Sites Australia, South Korea
Subjects Dose escalation stage: up to 18 patients; dose expansion stage: 24 patients
Status In progress
More Information

A phase 1/2a study to evaluate safety, pharmacokinetic and pharmacodynamic dose escalation and six month expansion study of PXS-5505 in patients with primary, post-polycythaemia vera or post-essential thrombocythemia myelofibrosis.

Commenced dosing February 2021


Media Releases

Other Indications for Oral Pan-LOX Inhibitor

Glioblastoma (MD Anderson (Houston) and Charlie Teo Foundation)

Pharmaxis and Charlie Teo Foundation Identify Promising New Drug to Tackle Brain Cancer: 

  • Read the media release here.
  • See the Channel Nine News story here: https://twitter.com/9NewsSyd/status/1388050205971566593?s=09
  • Watch an interview with CEO Gary Phillips here