On April 28, 2020 Pharmaceutical research company Pharmaxis Ltd (ASX: PXS) reported that following positive results from phase 1b and long term toxicity studies, the company is now progressing to a phase 2 study of its oral anti‐fibrotic pan‐Lysyl Oxidase (LOX) inhibitor PXS‐5505 for treatment of the rare bone cancer, myelofibrosis (MF) (Press release, Pharmaxis, APR 28, 2020, View Source [SID1234562006]).

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Pharmaxis has received pre IND feedback from the FDA on the PXS‐5505 program in MF and discussed the trial protocol with key opinion leaders in the US, Europe and Australia. Pharmaxis is currently preparing a full IND application for FDA submission mid‐year and appointing a Clinical Contract Research Organisation with a view to commencing recruitment in Q4 2020. The results of the phase 1b study of PXS‐5505 follow a successful phase 1a study reported in October 2019. The phase 1b was a double‐blind placebo controlled study in 16 healthy subjects divided into two groups with each group receiving a different dose or placebo daily for 14 days. The drug was well tolerated and no safety signals were identified during the study. Importantly for potential clinical benefit and in line with the phase 1a results, the data showed a drug with good pharmacokinetics and a dose related strong inhibition of members of the lysyl oxidase family in tissue and blood. PXS‐5505 is an oral drug that inhibits all lysyl oxidase family members (LOX, LOXL1, 2, 3 & 4). The compound successfully cleared pre‐clinical safety including 6‐month toxicity studies and has shown significant reductions in fibrosis in in‐vivo models of kidney, lung, heart, skin and liver fibrosis in addition to myelofibrosis and pancreatic cancer metastases. A recent publication1 reported that two Pharmaxis pan‐LOX inhibitor compounds have significantly decreased the bone marrow fibrotic burden in two different models of primary myelofibrosis. Myelofibrosis is a cancer with a poor prognosis and limited therapeutic options where only allogeneic stem cell transplantation is curative in a small number of patients who are eligible for such a treatment, while administration of a JAK1/2 inhibitor (e.g. ruxolitinib) provides mainly symptomatic relief but carries a risk of worsening blood cell counts. Pharmaxis CEO Gary Phillips said, "With the successful completion of the phase 1b study, 6‐month toxicity studies, support from clinical key opinion leaders and preliminary regulatory feedback, we can now move confidently into a 6‐month phase 2 study in myelofibrosis with meaningful clinical efficacy and safety endpoints. Pharmaxis believes that the current treatments for MF can be augmented by use of a pan‐LOX inhibitor and be disease modifying in a market that is conservatively worth US$1b per annum. We have ongoing discussions with contract research organisations who are confident of a trial recruitment start by the end of the year despite the impact of Covid‐19 on clinical trials worldwide. A number of contingency plans to maintain this timeline are actively being explored." Mr Phillips added, "The proprietary technology Pharmaxis has developed to measure activity and concentration of LOX and its related family members in tissue and blood enables us to clearly understand the role these enzymes have in fibrotic diseases and cancer and will significantly aid patient selection and proof‐of‐mechanism in the upcoming phase 2 trial. We are still gathering data from our academic collaborators who are investigating other cancers where fibrosis plays a significant role. These include pancreatic cancer, oral cancer, glioblastoma and mesothelioma where there is strong pre‐clinical evidence that several members of LOX family play a critical role." Pharmaxis will provide an update on phase 2 trial design once it has received final regulatory clearance in Q3 2020