Pharmaxis Ltd. announced that the scientific journal, Nature Communications, has published peer-reviewed data from a preclinical collaboration with University of Heidelberg investigating 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 PXS5505 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/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 5AZA and decitabine.

Although approximately 50% of MDS patients initially respond to HMAs, subsequent relapse is almost certain, highlighting an urgent need for compounds that significantly improve the beneficial effects of HMAs. Under the guidance of Professor WolfKarsten Hofmann and Professor Daniel Nowak, the team at Heidelberg University, Germany 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. This leads 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 PXS5505 plus 5AZA in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5AZA alone. The increases in red blood cells were confirmed using a xenograft model with transplanted patient's cells. This study also demonstrated normalization of spleen sizes, a reduction of bone marrow cells with severe mutations as well as significant reduction of disease burden.

The phase 2a trial MF101 in MF, cleared by the FDA under the Investigational New Drug (IND) scheme, aims to demonstrate that PXS5505 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 Second Quarter 23 to discuss the data from this study and the next steps in PXS5505 clinical development.