Clinical-stage drug development company Pharmaxis Ltd (ASX:PXS, OTC:PMXSF) has taken a leap forward in the fight against pancreatic ductal adenocarcinoma with its pan‐Lysyl Oxidase (pan‐LOX) inhibitor PXS‐5505 showing a 35% increase in survival rates compared to chemotherapy treatment alone.
The findings, published in the prestigious journal Nature Cancer, stemmed from rigorous pre-clinical trials led by the Garvan Institute of Medical Research in Sydney, Australia.
Apart from bolstering survival rates, the trials using mouse models showed PXS‐5505 reducing the spread of cancer to other organs such as the liver by 45% when combined with chemotherapy.
Major milestone
Pancreatic ductal adenocarcinoma is one of the most aggressive variants of pancreatic cancer, with a five‐year survival rate of less than 10%.
Garvan’s Matrix & Metastasis Lab head and senior author of the study Associate Professor Thomas Cox hailed the pre-clinical validation of PXS‐5505 as a seminal achievement in the quest to overcome the challenges of treating aggressive pancreatic cancer.
PXS‐5505, the first‐in‐class anti‐fibrotic pan‐LOX inhibitor, has undergone extensive toxicity evaluation and Phase 1a and 1b clinical trials, where it demonstrated its safety profile and its ability to effectively inhibit enzymes within the lysyl oxidase family involved in fibrosis.
“Ground‐breaking research”
“We have already seen very promising early results in a phase 2 trial with patients that have the bone marrow cancer myelofibrosis,” Pharmaxis chief executive officer Gary Phillips said.
“This ground‐breaking research stems from a long collaboration with the team of high-calibre researchers at the Garvan Institute and provides exciting new evidence that PXS‐5505 may also have a role as a therapy to improve the effect of current chemotherapy drugs in solid tumours like pancreatic cancer and extending the life of patients.”
A silent disease
Pancreatic cancer frequently eludes early detection, leading to diagnoses at advanced stages.
As a result, chemotherapy becomes the sole recourse for treatment but often patients develop a resistance to the treatment shortly after its initiation, leading to poor survival rates.
Part of this resistance is due to the development of tumour fibrosis, a mesh of scar tissue that forms within and around pancreatic tumours, which ultimately undermines the potency of chemotherapy drugs.
Adds to evidence
“PXS‐5505 returns the tumour microenvironment to a more ‘normal’ state by reducing fibrosis and decreasing tumour stiffness,” Garvan senior research officer and first author of the study Dr Jessica Chitty said.
“This allows chemotherapy drugs to penetrate the tumours more easily, work more effectively and destroy more cancer cells.”
The publication in Nature Cancer adds to the body of the drug’s pre‐clinical evidence published from other Pharmaxis collaborations with leading scientific institutions in the last year, including in Nature Communications 2023 and International Journal of Molecular Sciences 2022.