Antifungal Plant Defensins

Plant Defensin Antifungal Technology Platform

 

Hexima has identified several plant peptides with potent antifungal activity against a broad range of human and plant fungal pathogens. These peptides are all members of the plant defensin family.

Plant defensins represent a novel class of molecule with several attributes that make them suitable for use as drugs:

Stable

Their chemical structure makes them extremely stable and resistant to extremes of pH (<2) and temperature (>95°C), meaning that they are likely to be stable in a range of formulations.

Soluble

They are highly water soluble, eliminating the need for complex and toxic solvent systems in formulation.

Rapidly fungicidal

Defensins kill fungal cells, even with very short (<30 min) exposure.

Easy to produce

They can be produced using an off-patent yeast expression system and their small size and positive charge allows for a simple 2-step purification process which should allow for low-cost manufacture.

Plant defensins as novel fungal toenail infection treatments

Hexima has demonstrated that some defensins, such as its lead drug candidate, HXP124, can be formulated for efficient penetration through human nails. This makes HXP124 an excellent candidate for the treatment of onychomycosis, a fungal infection of the nail bed that most commonly occurs in toenails. Hexima is conducting a phase I/IIa clinical trial to assess the safety and preliminary efficacy of HXP124 as a novel topical treatment for fungal nail infections (onychomycosis). Hexima’s goal is to develop a topical fungal nail (onychomycosis) treatment with a superior cure rate, shorter treatment time and fewer side effects than existing oral and topical options.

Potential other applications

Hexima is also investigating the application of the plant defensin technology to other human fungal disease, in particular the control of medically important Candidaemias and Candida-based biofilms, particularly for topical applications such as oral and vaginal thrush.

Hexima has identified several plant defensins with the ability to kill Candida growing in a biofilm. Hexima will continue to assess the activity and safety profile of these defensins with the aim of progressing any promising candidates into pre-clinical proof-of-concept animal models. The Candida project is partially funded by a Science and Industry Endowment Fund STEM+ Business Fellowship awarded to Dr James McKenna. This fellowship allows Dr McKenna, an early career researcher based at the La Trobe Institute for Molecular Science (LIMS), to work with Hexima to investigate novel applications of the plant defensin technology.