Clinical stage drug development company Pharmaxis Ltd (ASX: PXS) today announced that an Investigational New Drug application (IND) for a trial of PXS-5505 in hepatocellular carcinoma (HCC) patients has been cleared by the United States Food and Drug Administration (FDA). The IND was submitted by the University of Rochester Medical Center, New York State, following the positive pre-clinical results reported in August 2021 at the Americas Hepato-Pancreato-Biliary Association conference in Miami, USA. The trial design approved by the FDA calls for PXS-5505 to be added to current chemotherapy standard of care; combination of a PD-L1 inhibitor and an anti-VEGF drug as first line therapy in newly diagnosed patients with unresectable HCC carcinoma.

Primary liver malignancies have doubled in incidence over the last two decades. These malignancies are now the 4th leading cause of cancer-related mortality worldwide with a 19.6% 5-year relative survival rates. Currently, just 20-30% HCC are resectable at presentation with many patients relying on chemotherapy. A prominent feature of HCC is the presence of highly fibrotic tissue that increases tumour stiffness, and decreases access of drugs into the tumour. Under the guidance of Dr. Roberto Hernandez-Alejandro, MD (Chief Division of Transplantation / Hepatobiliary Surgery), the research team at the University of Rochester Medical Center, New York State, have 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.

Dr. Roberto Hernandez-Alejandro said, "At the University of Rochester Wilmot Cancer Center, we are excited about the prospect of combining PXS-5505 with standard first line therapy for our unresectable hepatocellular carcinoma patients. The incidence of hepatocellular carcinoma is rising in part due to increasing incidence of cirrhosis and non-alcoholic steatohepatitis. Beyond resection, effective systemic therapies for this disease are lacking, thus new treatment regimens are of significant clinical need."

Dr. Nabeel Badri, (Wilmot Cancer Institute, University of Rochester) added, "PXS-5505 is a potent inhibitor of lysyl oxidase, a key enzyme in collagen crosslinking. By inhibiting the formation of fibrotic tissue in the tumor we hope to improve delivery and effectiveness of immunotherapy drugs which have so far had a limited impact of the survival of our patients. Through preclinical testing and translational research, we have developed a promising clinical trial design that has the potential to benefit these patients and improve our understanding of hepatocellular carcinoma."

The IND submitted by Rochester referenced the previous successful IND lodged by Pharmaxis for the ongoing phase 2 trial of PXS-5505 in myelofibrosis. The approved trial design envisages a dose escalation stage where the safety of PXS-5505 in combination with a PD-L1 inhibitor and an anti-VEGF drug will be assessed at several different doses as well as measures designed to explore the impact of PXS-5505 on fibrosis and drug perfusion. This will be followed by a 6-month trial of the selected dose with both safety and efficacy endpoints.

Pharmaxis CEO Gary Phillips said, "We highly value our collaboration with the research team at University of Rochester. The rapid progression from the compelling pre-clinical work presented for the first time in August to a successful IND submission is very encouraging and we look forward to concluding arrangements for the commencement of the dose escalation study in 2022. PXS-5505 has recently progressed to a phase 2 clinical trial looking for evidence of disease modifying effects in the bone cancer myelofibrosis as a monotherapy so exploring its additional potential to address cancers where fibrosis is limiting the clinical benefit of current chemotherapy- such as liver and pancreatic cancer- would be significantly value adding."