Clinical stage drug development company Pharmaxis Ltd (ASX: PXS) today announced the first public presentation of data from a preclinical study of PXS-5505 in the liver cancer, cholangiocarcinoma (CCA) at the Americas Hepato-Pancreato-Biliary Association (AHBPA) conference in Miami, USA.  

Under the guidance of Dr Roberto Hernandez-Alejandro, MD (Chief Division of Transplantation / Hepatobiliary Surgery), a research team at the University of Rochester Medical Center, New York State, has been investigating the role of lysyl oxidase enzymes in liver cancer and whether Pharmaxis cancer drug PXS-5505 can improve the efficacy of current chemotherapy drugs by inhibiting these enzymes.

CCA is the second most frequently diagnosed primary liver malignancy and has nearly doubled in incidence over the last decade. A prominent feature of CCA is the presence of highly fibrotic tissue that increases tumour stiffness, and decreases drug perfusion.

The oral presentation by Dr Paul Burchard, MD at today's meeting covered two main aspects of the team's research. 

• Firstly, they examined tumour tissue specimens collected from patients at their institution over a 10-year period and found that LOX enzymes are significantly elevated in human CCA and correlate with poor prognosis.
• Secondly, they examined the effect of PXS-5505 with or without chemotherapy treatment in a pre-clinical model of CCA and found that the combination of PXS-5505 and chemotherapy significantly improves survival, delays tumor growth, and reduces intratumoral pressure.
• Finally, they propose that PXS-5505 in combination with standard chemotherapy represents an innovative therapeutic strategy with potential for clinical translation in primary liver malignancy

Pharmaxis CEO Gary Phillips said, "The role of LOX enzymes in fibrosis is well established and there is a growing body of evidence that in cancers such as those of the liver and pancreas, the poor outcomes experienced with current chemotherapy regimens is due to fibrotic tissue restricting drug access and stimulating tumour growth.  Pharmaxis is working with a number of independent research groups globally on different tumour types with our anti fibrotic cancer drug PXS-5505 and I'm very encouraged by the results presented today by Dr Burchard that show a potential disease modifying role for our drug in liver cancer.

"PXS-5505 is currently progressing well through a phase 1c/2 clinical trial looking for evidence of disease modifying effects in bone cancer myelofibrosis as a monotherapy.  Exploring the potential of PXS-5505 to address liver cancers such as cholangiocarcinoma or other cancers where fibrosis is limiting the clinical benefit of current chemotherapy is something we will continue to assess with our scientific and clinical collaborators."

The phase 1c/2a trial MF-101 in myelofibrosis, 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.