Investigating the Safety and Tolerability of a Lysyl Oxidase Inhibitor (PXS-6302) vs Placebo in the Amelioration of Established Scars.

Natalie Morellini¹, Helen Douglas^1,2, Suzanne Rea^1,2, Wolfgang Jarolimek³, Fiona Wood^1,2, Mark Fear¹,
¹Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia
²Burns Service of Western Australia, WA, Department of Health, Nedlands, Western Australia, Australia
³Drug Discovery Department, Pharmaxis Ltd, Sydney, NSW, Australia

Abstract

BACKGROUND: Lysyl oxidases are a family of enzymes that play a critical role in scar formation, maintenance and fibrosis. Lysyl oxidases stabilize the main component of scar and fibrotic tissue, collagen, through cross-linking. This cross-linking renders the collagen less soluble and less susceptible to degradation, leading to increased stiffness of tissue in scar and fibrosis. We have developed a new irreversible inhibitor of all Lysyl oxidases, PXS-6302. We have conducted initial phase I studies of PXS-6302 to assess safety, target engagement and potential for the treatment of scarring and fibrosis.
METHODS: A total of 50 participants with established scars (>1 year) were enrolled in a double-blinded randomized clinical trial. Participants either applied PX-6302 or Placebo cream to a 10cm2 area of scar over a period of three months and were assessed at monthly intervals for safety and changes in the scar. Blood samples and skin biopsies were collected at day 1 and at three months to measure systemic absorption of PXS-6302 and changes in the extracellular matrix of the scar.
RESULTS: Initial phase I studies demonstrated lysyl oxidase inhibition in skin and negligible systemic absorption. Preliminary data suggests changes in the extracellular matrix and associated proteins consistent with scar improvement in participants with established scars. Final analysis of an RCT in established scars is ongoing.
CONCLUSION: This study demonstrates that PXS-6302 is safe and targeting lysyl oxidases may present an effective approach in the treatment of scar.

Biography

Completed a PhD in burn repair and nerve regeneration at the University of Western Australia in 2010. Worked as a post-doctoral researcher at The Sorbonne University in Paris to investigate neuroplasticity in the aging brain and Murdoch University in Perth to investigate chronic pain. Joined the Burns research team again in 2021.