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 myelofibrosis, myelodysplastic syndrome, pancreatic cancer, kidney fibrosis and lung fibrosis,. 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 is initially developing 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)

Presentations at the Pharmaxis R&D Showcase Webinar in March 2021:

  • Dr Gabriela Hobbs (Massachusetts General Hospital) on the myelofibrosis landscape and MF-101 can be seen here.
  • Dr Paul Burchard (Rochester NY) on Hepatocellular cancer and details of the Rochester University investigator led study can be seen here.
  • Dr Tom Cox (Garvan Sydney) on pancreatic cancer and his preclinical work on PXS-5505 can be seen here.


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 clinical trial was conducted at sites in Australia and South Korea, and studied PXS-5505 in patients with the bone marrow cancer myelofibrosis for 28 days at three dosage levels.  The trial reported in October 2021. Assessment with Pharmaxis’ proprietary assays of the highest dose demonstrated inhibition of the target enzymes, LOX and LOXL2, at greater than 90% over a 24‐hour period at day 7 and day 28. The trial safety committee identified no safety signals and cleared the study to progress to the phase 2a dose expansion phase where 24 patients will be treated at the highest dose twice a day for 6 months. Read the media release here.

The phase 2a commenced in October 2021 and is being conducted at sites in Australia, South Korea, Taiwan and the United States. Read the media release here.

In October 2022 Pharmaxis announced positive interim data – read the media release here.

In July 2023 Pharmaxis reported the final interim analysis of data from 10 myelofibrosis patients who had completed 6 months’ treatment with PXS‐5505 in the open label phase 2 clinical trial. 60% of patients showed improvement in fibrosis with the data also demonstrating an excellent safety profile and promising signs of clinical activity. Read the media release here.

Myelodysplastic Syndrome (MDS)

The potential use of PXS-5505 in myelodysplastic syndrome was the subject of a poster presentation at the 2022 American Society of Hematology conference (ASH) in in December 2022. The poster reported on ground breaking work done in collaboration with Professor Wolf‐Karsten Hofmann and Professor Daniel Nowak at Heidelberg University, Germany. The preclinical models combined PXS-5505 and the standard of care (5-azacytidine) and were reported in Nature Communications in March 2023. The paper concludes that the work makes a strong case for trialling the combination in MDS patients, especially those who are anaemic. Read more here.

Liver Cancer

The combination of PXS-5505 and standard of care in preclinical models demonstrates a novel therapeutic strategy for liver cancer. Data presented from collaboration of Pharmaxis and University of Rochester Medical Center at US Scientific Meeting. Read more here.

A planned investigator initiated clinical trial by the University of Rochester in hepatocellular carcinoma (HCC) patients will not progressed at this point as Pharmaxis focusses its resources on haematological malignancies such as MF and MDS.

Pharmaxis collaboration with the research team at University of Rochester continues with further pre-clinical evaluation of Pharmaxis pipeline assets.

Access Pharmaxis Publications and Posters on LOX inhibitors

·        Myelodysplastic syndrome

·       Liver Cancer
Rochester (NY)

·       Pancreatic Cancer
Sydney (Garvan Institute of Medical Research), Rochester (NY)



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, Taiwan, USA
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