Pharmaxis Ltd (ASX:PXS, OTC:PMXSF) welcomes the presentation of two scientific posters at the American Society of Haematology Conference (ASH) in New Orleans, along with discussions with the FDA and a new study in train.
The posters deliver clinical evidence on the disease modifying effect of the clinical-stage drug development company’s pan LOX inhibitor PXS-5505 in bone marrow cancer, and pre-clinical evidence in other myeloid neoplasms.
Poster 1 showed interim data from the ongoing Phase 2 myelofibrosis study (MF-101) that reinforced the conclusions reported in October for the first six patients to have completed six months of treatment.
Disease stabilisation
It demonstrated that PXS-5505 is well-tolerated and that clinical responses support continued investigation in myelofibrosis within no dose-limiting toxicity observed and preliminary indication of disease stabilisation.
The drug demonstrates potent and sustained inhibition of lysyl oxidases in patients with five out of six patients either stable or showing improved bone marrow fibrosis scores of greater than 1 grade.
These results are encouraging given the poor prognosis seen after ruxolitinib discontinuation with a median overall survival of only 11 to 14 months typical of this study population.
The poster detailed the haematological response to PXS-5505 in six patients, five of whom had stable or improved haemoglobin counts, including one patient that had an anaemia response (Hgb increase greater than 20 g/L) at week 18 with no red blood cell transfusions, and five of whom had stable or improved platelet counts over 24 weeks of therapy.
Therapeutic target
Poster 2, 'Inhibition of Lysyl Oxidases Synergises with 5-Azacytidine to Restore Erythropoiesis in Myeloid Neoplasms', reported on ground-breaking work done in collaboration with Professor Wolf-Karsten Hofmann and Professor Daniel Nowak at Heidelberg University, Germany.
This poster outlines how, given the limited response rates and frequent relapses during currently approved drug treatments in myeloid neoplasms, an urgent unmet need exists in diseases such as myelodysplastic syndrome.
The altered bone marrow niche in myeloid neoplasms is increasingly being recognised as a therapeutic target where up-regulated lysyl oxidase activity contributes to the excessive deposition of extracellular matrix proteins.
The full results will be the subject of a future publication. The American Society of Haematology conference in New Orleans is one of the premier gatherings of scientists and clinicians in this field of research and this year it was attended by more than 20,000 people.
Discussions with FDA
Pharmaxis CEO Gary Phillips said: “It is very encouraging to see so many positive responses at ASH to the pioneering work Pharmaxis has been conducting in the role of lysyl oxidase in a variety of diseases.
"For our pan-LOX inhibitor, PXS-5505, there is increasing data that we have a safe and well-tolerated drug achieving high target engagement and with the potential to make a real difference to patients, not only in myelofibrosis but also other myeloid neoplasms.
"Based on the ongoing data from MF-101 we will schedule discussions with the FDA in Q1 2023 on the next steps of clinical development for PXS-5505 in myelofibrosis.”
PXS-5505 in new study
While the company’s primary focus is the development of PXS-5505 for myeloid neoplasms such as myelofibrosis and myelodysplastic syndrome, the drug also has potential in several other cancers including liver and pancreatic cancer where it has the potential to break down the fibrotic tissue in tumours and enhance chemotherapy treatment.
An investigator-led Phase 1c study in newly diagnosed hepatocellular cancer patients, where PXS-5505 will be used in addition to immunotherapy standard of care, is open for recruitment at Rochester University in New York.