Human Antifungal

Hexima is focused on the research and development of plant-derived molecules for use in human health and agriculture.

The Company has a strategic goal to develop a best-in-class topical treatment for onychomycosis (fungal nail infections) with a superior cure rate, shorter treatment time and fewer side effects than existing oral and topical options. Hexima’s antifungal technology is likely to be applicable to a broader range of human and plant fungal diseases.

Hexima is conducting a phase I/IIa clinical trial to assess the safety and preliminary efficacy of its lead antifungal molecule, HXP124 as a treatment for onychomycosis.

Plant Defensin Antifungal Technology Platform

Hexima has identified several plant peptides (including HXP124 and HXP4, a variant of the NaD1 peptide originally patented by Hexima with improved activity) 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

Rapidly fungicidal

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

Soluble

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

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.

Onychomycosis

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An onychomycosis affected nail showing discolouration of the nail plate.
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An onychomycosis affected nail showing discolouration of the nail plate.

Onychomycosis is an infection that can cause toenails and fingernails to thicken, discolour, split or disfigure. Dermatophytic, or fungal, infection is the most common cause of onychomycosis, and toenails are most commonly affected. Although the infection may initially be of aesthetic concern only, without treatment, nails can thicken and disfigure to the extent they cause irritation, pain and difficulty walking.

The most common type of onychomycosis is distal lateral subungual onychomycosis (DLSO), In DLSO cases, the fungus spreads from skin on the feet and invades the nail bed via the hyponychium. Inflammation occurring in these areas of the nail causes the typical physical signs of DLSO.

The most common type of onychomycosis is distal lateral subungual onychomycosis (DLSO), In DLSO cases, the fungus spreads from skin on the feet and invades the nail bed via the hyponychium. Inflammation occurring in these areas of the nail causes the typical physical signs of DLSO.
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A schematic representation of a toenail showing the nail plate covering the nail bed, the main site of fungal infection.
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A schematic representation of a toenail showing the nail plate covering the nail bed, the main site of fungal infection.
The two main treatment regimens for onychomycosis are topical and oral anti-fungal therapies. Current topical treatments offer limited efficacy because they either cannot penetrate the nail sufficiently to reach the infection site under the nail, or they only slow rather than kill fungal growth. Treatment times are long (up to a year) and topical treatments are generally unable to completely cure the infection. Oral treatments are more effective as they can reach the infection site systemically and offer shorter treatment times (usually three months). However, oral anti-fungal treatments are associated with serious side effects and consequently, are not recommended for those with liver disease or heart conditions. Furthermore, about 20-25% of patients fail to respond to oral drugs.

HXP124

Hexima’s goal is to develop a topical onychomycosis treatment with a superior cure rate, shorter treatment time and fewer side effects than existing oral and topical options.

See Hexima’s lead clinical asset, HXP124.