Pharmaxis’ first results in bone marrow cancer trial show strong inhibition of target enzymes

Pharmaxis Ltd’s (ASX:PXS) (FRA:UUD) first results from a three-stage phase 1c clinical trial (MF-101) studying a potential treatment for bone marrow cancer myelofibrosis, have demonstrated strong inhibition of target enzymes LOX and LOXL2 in patients. The phase 1c/2a trial MF-101 cleared by the 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. An effective pan-LOX inhibitor for myelofibrosis would open a market that is conservatively estimated at US$1 billion per annum. While Pharmaxis’ primary focus is the development of PXS-5505 for myelofibrosis, the drug also has potential in several other cancers including liver and pancreatic cancer, where it aims to breakdown the fibrotic tissue in the tumour and enhance the effect of chemotherapy treatment. PXS shares have been as much as 32% higher to A$0.099 intra-day. “Delighted” with results Chief executive officer Gary Phillips said: “We are delighted to see that along with excellent tolerability, we are achieving levels of LOX and LOXL2 inhibition in myelofibrosis patients that are already exceeding those levels seen in the preclinical models of myelofibrosis. “In these models, PXS-5505 caused disease modifying effects with improvements in blood cell count, diminished spleen size and reduced bone marrow fibrosis. “Comparing these results with those achieved in the phase-1 study with healthy volunteers, we are now very confident that we will achieve a level of inhibition of the lysyl oxidase enzyme family that will allow us to fully test the clinical relevance of these targets in myelofibrosis patients in the upcoming 6-month dose expansion study.” Successful recruitment The second dose cohort of the clinical trial is already fully recruited, and dosing of all patients has begun at participating sites in Australian and South Korean hospitals. Following 28 days on this second dose, the safety and pharmacokinetics will be assessed before starting myelofibrosis patients on the final and highest dose. The dose escalation phase of the study will inform the selection of the optimal dose of PXS-5505 to be used in the six-month dose expansion to evaluate safety and efficacy which is expected to report results by the end of 2022. Sites in other countries, including the USA are currently being engaged in anticipation of the dose expansion phase commencing recruitment later this year.