Clinical stage drug development company Pharmaxis (ASX:PXS) reports that peer review data from a preclinical collaboration with the University of Heidelberg has been published in the Nature Communications scientific journal.

The company reports this study investigated the role of lysyl oxidase enzymes in myelodysplastic syndrome (MDS) and the effect of combining 5-azacytidine (5-AZA) with Pharmaxis’ pan-lysyl oxidase inhibitor, PXS-5505.

The authors conclude that the ‘significant’ increase in red blood cell production evidenced in their studies makes a strong case for trialling PXS-5505 combined with the current standard of care in MDS patients, especially those who are anaemic.

“This is a compelling body of research gathered over a multi-year collaboration between Heidelberg University and Pharmaxis…”

MDS comprises a group of blood cancers that share clinical and pathologic features with acute myeloid leukaemia (AML). MDS occurs most commonly in older adults with an annual incidence thought to be as ‘high’ as 75 cases per 100,000.

Patients with MDS are at risk of symptomatic anaemia, infection, bleeding, and transformation to AML. The current standard of care for ‘high-risk’ MDS is treatment with hypomethylating agents (HMAs) such as 5-AZA and decitabine.

Although about 50% of MDS patients initially respond to HMAs, subsequent relapse is almost certain which highlights an ‘urgent’ need for compounds that significantly improve the beneficial effects of HMAs.

Under the guidance of Professor Wold-Karsen Hofmann and Professor Daniel Nowak, the team at Heidelberg University in Germany reported that all LOX/LOXL genes except for LOXL1 were significantly overexpressed in bone marrow cells derived from patients with MDS and other related haematological malignancies when compared to healthy controls. This leads to a corresponding increase in lysyl oxidase activity.

The team also reports the formation of red blood cells from bone marrow taken from these patients is significantly restored when treated with PXS-5505 plus 5-AZA in 20 out of 31 cases versus 9 in 31 cases treated with 5-AZA alone.

The increases in red blood cells were confirmed using a xenograft model with transplanted patient’s cells. This study also demonstrated normalisation of spleen sizes, a reduction of bone marrow cells with severe mutations, as well as ‘significant’ reduction of disease burden.

Commenting on the results, Pharmaxis Chief Executive Officer Gary Phillips said: “This is a compelling body of research gathered over a multi-year collaboration between Heidelberg University and Pharmaxis that extends the potential for PXS-5505 to treat haematological malignancies beyond myelofibrosis where we have recently reported encouraging preliminary phase two clinical trial data.

There will be updated in Q2 2023 as more patients complete 6 months treatment and we get feedback from the FDA (US Food and Drug Administration) on progressing the development of PXS-5505 in myelofibrosis.”

Also commenting, Heidelberg University Professor Daniel Nowak says: “This study is one of the first published showing that remodelling the extracellular matrix and bone marrow microenvironment can induce outstanding improvements of haematopoiesis in the diseases.

The results of PXS-5505 in combination with 5-AZA are the best we have ever observed in our preclinical models of MDS with primary patient samples.

The significant boost in erythropoiesis achieved by adding PXS-5505, allied to its favourable safety profile makes the combination of 5-AZA and PXS-5505 interesting for both high and low risk MDS as well as chronic myelomonocytic leukaemia, myelofibrosis, and low blast acute myeloid leukaemia, filling a significant gap in the current treatment landscape of these diseases.”

Pharmaxis reports the phase two a trial MF-101 in MF, which has been cleared by the US Food and Drug Administration (FDA) under the Investigational New Drug (IND) scheme 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.

This trial is now over 80% recruited and Pharmaxis has scheduled a review meeting with the FDA in Q2 2023 to discuss the data from this study and the next steps in PXS-5505 clinical development.

Pharmaxis is an Australian clinical stage development company focused on developing drugs for inflammatory and fibrotic diseases.