Alterity Therapeutics (ATH) Corporate Presentation summary

Company overview and strategy

• Focuses on developing treatments for neurodegenerative diseases, aiming to slow disease progression and improve patient quality of life.

• Lead candidate ATH434 targets multiple system atrophy (MSA), a Parkinsonian disorder with no approved treatments.

• Holds Fast Track and Orphan Drug Designations for ATH434 in the US and EU.

• Leadership team has extensive experience in neurology and movement disorders.

• Strong cash position of A$40.7M as of June 30, 2025.

Scientific rationale and mechanism of action

• Pathology in MSA and Parkinson's involves α-synuclein aggregation and iron imbalance, leading to neurotoxicity.

• Excess reactive iron promotes α-synuclein aggregation and oxidative injury, causing neuron death.

• ATH434 is a small molecule iron chaperone that redistributes excess labile iron in the CNS, reducing α-synuclein aggregation and oxidative stress.

• Oral administration is preferred over infusions or injections.

Clinical development and trial results

• Phase 2 double-blind trial (ATH434-201) in MSA showed clinically significant efficacy on the FDA-endorsed UMSARS I functional endpoint.

• 50 mg dose reduced UMSARS I worsening by 48% vs placebo (p=0.02); 75 mg dose showed a 30% reduction (p=0.16).

• Improvements observed in Clinical Global Impression of Severity (p=0.009) and trends in orthostatic hypotension and activity levels.

• MRI biomarkers confirmed target engagement with reduced iron accumulation in affected brain regions.

• ATH434 was well-tolerated with adverse event rates similar to placebo and no treatment-related safety signals.