Alterity Therapeutics Limited announced that important new data on its lead drug candidate ATH434 was presented at the World Orphan Drug Congress USA 2024 in Boston, MA. The poster, entitled, ?Biophysical Characteristics of ATH434, a Unique Iron-Targeting Drug for Treating Friedreich?s Ataxia?, was presented by Ashley Pall, Department of Pharmaceutical Sciences at Wayne State University. The study evaluated the ability of ATH434 to target the toxic form of iron that drives the pathology of Friedreich?s Ataxia, a rare neurodegenerative disease that affects young children to young adults.

The study also evaluated traditional iron chelators that are designed to bind iron and remove iron from the body. Conversely, an iron chaperone is designed to bind and redistribute iron within the body. Specifically, the study investigated how strongly ATH434 or traditional iron chelators bind the two forms of cellular iron: ferric iron, the stored form, or ferrous iron, the form required for vital cellular functions such as energy production.

In excess, the ferrous or ?labile? iron can also promote oxidative stress in diseases like Friedreich?s Ataxia as it does in Parkinson?s disease and Multiple System Atrophy. The novel iron binding properties of ATH434 presented in the poster support the characterization of ATH434 as an iron chaperone based on properties it shares with endogenous iron chaperones such as frataxin and poly-C binding proteins.

These include its low micromolar binding affinity for ferrous iron and a bound structure that may allow for transfer of ferrous iron proteins involved in cellular function. The new data also confirmed that ATH434 has a dramatically lower affinity for ferric iron than traditional iron chelators that are approved for treating systemic iron overload. Together, these properties suggest that ATH434 has the capacity to selectively target pathogenic ferrous iron without impairing normal cellular iron trafficking or functions.

Alterity?s lead candidate, ATH434, is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration. ATH434 has been shown preclinically to reduce a-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain. As an iron chaperone, it has excellent potential to treat Parkinson?s disease as well as various Parkinsonian disorders such as Multiple System Atrophy (MSA).

ATH434 successfully completed Phase 1 studies demonstrating the agent is well tolerated and achieved brain levels comparable to efficacious levels in animal models of MSA. ATH434 is currently being studied in two clinical trials: Study ATH434-201 is a randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage MSA and Study ATH434-202 is an open-label Phase 2 Biomarker trial in patients with more advanced MSA. ATH434 has been granted Orphan drug designation for the treatment of MSA by the U.S. FDA and the European Commission.