Prestigious scientific journal Nature Communications has featured Pharmaxis Ltd (ASX:PXS, OTC:PMXSF)’s peer-reviewed data from a preclinical collaboration with the University of Heidelberg that demonstrates a strong rationale for the treatment of several blood cancers.
The trial investigates 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‐55051.
Significant increase in red blood cells
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.
MDS comprises a group of blood cancers that share clinical and pathologic features with acute myeloid leukemia (AML).
MDS occurs most commonly in older adults with an annual incidence thought to be as high as 75 cases in 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 some 50% of MDS patients initially respond to HMAs, subsequent relapse is almost certain. This highlights an urgent need for compounds that significantly improve the beneficial effects of HMAs.
Findings
The team at Heidelberg University, Germany, under the guidance of Professor Wolf‐Karsten Hofmann and Professor Daniel Nowak, has 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, leading to a corresponding increase in lysyl oxidase activity;
- formation of red blood cells from bone marrow taken from these patients is significantly restored when treated with PXS‐5505 plus 5‐AZA in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5‐AZA alone; and
- the increases in red blood cells were confirmed using a xenograft model with transplanted patient’s cells.
Professor Nowak said, “This study is one of the first published showing that re‐modelling the extracellular matrix and bone marrow microenvironment can induce outstanding improvements of haematopoiesis in these diseases.
“The results of PXS‐5505 in combination with 5‐AZA are the best we have ever observed in our pre‐clinical 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 Page 2 of 3 chronic myelomonocytic leukemia, myelofibrosis and low blast acute myeloid leukemia, filling a significant gap in the current treatment landscape of these diseases.”
Pharmaxis CEO 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 2 clinical trial data.
“There will be updates in Q2 2023 as more patients complete six months’ treatment and we get feedback from the FDA on progressing the development of PXS‐5505 in myelofibrosis.”
Phase 2a trial
The Phase 2a trial MF‐101 in MF, cleared by the 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 more than 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 the clinical development of PXS‐5505.