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Overview of Pipeline Opportunities in the Clinic for Fibrosis and Inflammation

Pan-LOX inhibitor PXS-5505

(indications in addition to myelofibrosis) 
  • Targeting myelodysplastic syndrome (MDS) and hepatocellular carcinoma (HCC) - the most common type of primary liver cancer.
    • Preclinical models combining PXS-5505 and the standard of care (5-azacytidine) makes a strong case for trialling the combination in MDS patients, especially those who are anaemic. Peer reviewed data from a preclinical collaboration with University of Heidelberg investigating the role of lysyl oxidase enzymes in MDS and the effect of combining 5-azacytidine with Pharmaxis’ pan-lysyl oxidase inhibitor, PXS-5505 was reported in Nature Communications. Read more here.
    • The combination of PXS-5505 and standard of care in preclinical models demonstrates a novel therapeutic strategy for liver cancer. Data presented from collaboration of Pharmaxis and University of Rochester Medical Center at US Scientific Meeting. Read more here.
  • More information here

Topical pan-LOX inhibitor PXS-6302

  • Anti scarring: burns, established scars
  • Status:
    • Pharmaxis treatment for established scars clears phase 1 trial (read more here)
    • First patient dosed in phase 1c trial of Pharmaxis scar reduction drug (read more here)
    • Promising interim data from clinical trial released (read more here)
  • More information here

LOXL2 inhibitor PXS-5382

  • Anti fibrotic targeting chronic kidney disease (CKD), pulmonary fibrosis (IPF) and non-alcoholic steatohepatitis (NASH)
  • Status:
    • phase 2 ready program
    • partnering discussions
    • phase 2 protocol and funding discussions with independent investigators
  • More information here

SSAO inhibitor PXS-4728

  • Anti inflammatory: neuro inflammation
  • Status:
    • Ground-breaking Pharmaxis collaboration with Parkinson’s UK and leading neurologists to investigate PXS-4728 to treat patients at risk of Parkinson’s and other neurodegenerative diseases.

    • The £2.9m funding comes from the Parkinson’s Virtual Biotech programme.
    • Collaborators at Sydney and Oxford universities to lead the study.
    • Pharmaxis team continues to deliver commercial deals leveraging expertise in inflammation.
    • Clinical trial to begin recruiting patients mid 2023. 
  • More information here
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Pharmaxis Clinical Trial Targets Bone Marrow Cancer Treatment

Pharmaxis is advancing clinical trials of a new drug (PXS-5505) targeting the rare bone marrow cancer myelofibrosis (MF). A phase 2a open label trial commenced dosing in October 2021 and has recruited 21 adult patients in an open label study of patients who are not on a JAK inhibitor.

PXS-5505 was granted Orphan Drug Designation by the US Food and Drug Administration (FDA) in July 2020. Read the media release.

In April 2023, Pharmaxis announced it would expand the study to also include patients receiving a JAK inhibitor - the current standard of care. This followed feedback from the FDA which reviewed positive interim safety and efficacy data from the monotherapy trial. Read the release here.

Participating trial site locations include Australia, Taiwan, South Korea and the USA. The aim of the phase 2 trial is to show PXS-5505 is safe to be taken longer term with the disease modifying effects seen in the pre-clinical models. The study is proceeding under an Investigational New Drug application cleared by the US FDA. Read more here.

Assessment with Pharmaxis’ proprietary assays of the highest dose in the preceding phase 1c trial showed inhibition of the target enzymes, LOX and LOXL2, at greater than 90% over a 24-hour period at day 7 and day 28. Pre-clinical work has established PXS-5505 causes disease modifying effects with improvements in blood cell count, diminished spleen size and reduced bone marrow fibrosis. Read more here.

PXS-5505 is an anti‐fibrotic pan-Lysyl Oxidase (pan-LOX) inhibitor that has completed long-term toxicity studies and Phase 1a and 1b clinical trials demonstrating a well-tolerated drug that effectively inhibits all enzymes in the lysyl oxidase family that are involved in fibrosis.

Myelofibrosis is a cancer with a poor prognosis and limited therapeutic options. Pharmaxis believes that the current treatments can be augmented by use of a pan-LOX inhibitor and be disease modifying in a market that is conservatively worth US$1 billion per annum.

A study published by researchers at Boston University School of Medicine found that the two Pharmaxis drug discoveries PXS-LOX_1 and PXS-LOX_2 showed promising early results in slowing disease progression in primary myelofibrosis (PMF). Read more here: https://www.eurekalert.org/pub_releases/2021-03/buso-bri032221.php

In July 2023 Pharmaxis reported the final interim analysis of data from 10 myelofibrosis patients who had completed 6 months’ treatment with PXS‐5505 in the open label phase 2 clinical trial. 60% of patients showed improvement in fibrosis with the data also demonstrating an excellent safety profile and promising signs of clinical activity. Read the announcement here.


Recent Highlights

Syntara has announced the first patient has been dosed in its randomised double-blind placebo controlled Phase 2 study of the Syntara drug discovery PXS-4728 studying patients with isolated Rapid Eye Movement Sleep Behaviour Disorder (iRBD) who are at risk of Parkinson’s disease. The study will examine whether targeting inflammation in the brain of people with iRBD might provide a viable neuroprotective strategy to prevent Parkinson’s and other neurogenerative diseases. The multi-national trial is majority funded by the Parkinson’s Virtual Biotech, the international drug discovery and development program founded by Parkinson’s UK. Read more here

Pharmaxis 2023 Annual General Meeting

28 November 2023 at 11.00am. Details here.

Sale of mannitol respiratory business and launch of Syntara

Pharmaxis has announced details of the sale of its mannitol respiratory business which manufactures and supplies Aridol and Bronchitol to global markets and the formation of Syntara, a clinical stage drug development company primarily focusing on treatments for haematological malignancies (blood-related cancers).

In a major restructure the mannitol business will be sold to pharmaceutical manufacturing specialist, Arna Pharma  with residual net exit costs of less than A$1m. and core expenses reduced by more than 60%, saving the company over A$14m per year.

Syntara will have five planned clinical studies to deliver results in high unmet need diseases by mid-2025. (The new company name is subject to approval by shareholders at the company AGM in November.)

Read more here.
Watch an interview with CEO Gary Phillips outlining the changes here.

Publication in Nature Cancer 

The prestigious journal Nature Cancer has published preclinical results showing Pharmaxis’ pan-Lysyl Oxidase (pan-LOX) inhibitor PXS-5505 increases survival by 35% compared to chemotherapy treatment alone in the treatment of pancreatic ductal adenocarcinomas.

Research in mouse models, led by a team at the Garvan Institute of Medical Research also showed PXS-5505 combined with chemotherapy reduced the spread of the cancer to other organs such as the liver by 45%.

Read more here:

Watch the 9 News national story here: https://twitter.com/9NewsSyd/status/1696445007635374495

60% of patients show improvement in fibrosis in Pharmaxis myelofibrosis phase 2 cancer trial.

Final set of interim data from PXS-5505 trial in 10 patients treated for 6 months demonstrates improvements in fibrosis grade, excellent safety profile and promising signs of clinical activity.

Read more here.
Watch an interview with CEO Gary Phillips here.

Pharmaxis Cancer Drug Doubles Response Rate to Standard Therapy in Blood Cancer Pre Clinical Studies

Nature communications publishes peer-reviewed data from highly predictive pre clinical models using cells from mylodysplastic syndrome patients.

Best in class results from combination of pxs-5505 and standard of care demonstrates a strong rationale for treatment of several blood cancers.

Read more here.

Pharmaxis achieves 30% reduction in scar tissue in topical LOX inhibitor in Phase 1C study; extends collaboration with UWA

Pharmaxis’ novel topical drug treatment for scarring has achieved encouraging results from a phase 1c showing marked change in scar composition with 30% reduction in collagen content. The study of LOX inhibitor PXS-6302 is being conducted by the University of Western Australia (UWA) under the leadership of Professor Fiona Wood AM.  The study aims to improve the appearance and function of established scars by tackling the enzyme that plays a critical role in crosslinking collagen fibres in scar formation.

The phase 1c study met its primary safety objective and two secondary biomarker endpoints in patients with established scars, providing first ever proof that LOX inhibition reduces skin collagen.

Read more here.
See Proactive Investors interview with CEO Gary Phillips here

Recent interviews and articles:  

  • Proactive Investors, " CEO Gary Phillips speaks with Proactive after releasing data from a final interim analysis of 10 patients who have completed six months’ treatment with its drug PXS-5505 in an open label phase 2 clinical trial in patients with the bone marrow cancer myelofibrosis. The data points to an excellent safety profile and promising signs of clinical activity, with 60% of patients who reached the six-month mark showing improved bone marrow fibrosis scores." (13 July 2023). Watch the interview here.
  • Proactive Investors, "CEO Gary Phillips tells Proactive the company has made great progress towards commercialisation in a Phase 1C study of its topical Pan LOX inhibitor, achieving a well-tolerated safety profile and a marked change in scar composition. Importantly, the study’s results mark the first-ever proof that LOX inhibition reduces skin collagen, having achieved a 30% reduction in the scar’s collagen content." (25 May 2023) Watch the interview here.
  • Proactive Investors: "CEO Gary Phillips tells Proactive the company will add a combination treatment arm to the current Phase 2 clinical trial of PXS‐5505 in myelofibrosis following helpful feedback from the US FDA. He says they’re already in discussion with the existing trial site investigators who have welcomed the opportunity to extend the patient population for the study and anticipate significantly accelerated recruitment." (12 April 2023). Watch the interview here.