Posted: 1 May 2024
Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to developing disease modifying treatments for neurodegenerative diseases, today 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.
“This investigation provides important insights into the mechanism of action of ATH434, namely that it selectively targets the labile iron implicated in the pathology of important neurodegenerative diseases. In this way, ATH434 behaves like a chaperone to redistribute iron within the body. There has historically been great interest in targeting iron in general to treat these diseases, and we now have clear evidence that ATH434 is very different from traditional iron chelators,” said, David Stamler, M.D., Chief Executive Officer of Alterity.
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.
Dr. Stamler continued, “The genetic defect in Friedreich’s Ataxia leads to reduced function of frataxin, a protein necessary for utilizing labile iron, thus leading to iron accumulation in disease. By acting as an iron chaperone, ATH434 has potential to reduce labile iron levels and thus slow disease progression. Given these new data, we are excited to evaluate FA as a potential new indication for ATH434.”
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.
The poster presentation can be found on Alterity’s website here.
