Alterity Therapeutics presents data on ATH434 at MDS Congress

Alterity Therapeutics announced that multiple oral and poster presentations were presented at the International Congress of Parkinson’s Disease and Movement Disorders. Title: Preliminary Efficacy and Safety of ATH434 in Multiple System Atrophy: Results: The interim data suggest that ATH434 may have a disease-modifying effect in MSA, with 30% of participants showing stable or improved clinical outcomes. The average change in Unified MSA Rating Scale Part I scores over 6 months is smaller than typically observed in untreated MSA patients. At 6 months all participants exhibited brain volume declines consistent with MSA progression; however, the clinical responders maintained stable brain volumes at 12 months. Importantly, ATH434 was well tolerated with no drug-related serious adverse events, and most adverse events were mild to moderate, showing a favorable safety profile. Together, these early outcomes suggest that ATH434 could have a potential to modify disease progression. Neurofilament light chain levels are a measure of neuronal injury and are often correlated with disease severity. In the Phase 2 trial, the clinical responders had stable or reduced NfL levels: at 6 months, the average increases in NfL were 2.7% in CSF and 4.5% in plasma, compared to 17.9% and 19.3% in Alterity’s bioMUSE natural history participants, respectively. In addition, clinical responders also showed stability in iron levels in the substantia nigra, putamen, and globus pallidus compared to non-responders with increased iron. The stabilization of iron content in these subcortical brain regions, combined with NfL biomarker data, indicates that ATH434 may slow neurodegeneration by modulating brain iron levels and reducing oxidative injury. Title: A Phase 2 Study of ATH434, a Novel Inhibitor of alpha-Synuclein Aggregation, for the Treatment of Multiple System Atrophy: Results: The oral presentation and poster describe the baseline characteristics for the 77 participants from Alterity’s ATH434-201 randomized, double-blind Phase 2 clinical trial, with a focus on baseline fluid biomarkers, neuroimaging and clinical data. The participants met strict selection criteria designed to confirm that participants had early-stage MSA. The accuracy of diagnosing clinically probable MSA may be increased using a multimodal approach that includes neuroimaging biomarkers and fluid biomarkers such as NfL. ATH434 is a potential disease modifying therapy based on its ability to redistribute excess labile iron without impairing normal iron storage, inhibit alpha-synuclein aggregation and reduce oxidative injury. Importantly, increased iron levels were evident in multiple subcortical brain regions, with increased levels being observed in the substantia nigra in nearly all subjects. Title: Association Between Clinical Progression in Multiple System Atrophy and Brain Volume Changes Evaluated via Deep Learning Segmentation: Results: The poster describes results from the “Biomarkers of progression in Multiple System Atrophy” natural history study designed to track the progression of individuals with MSA. For participants enrolled in bioMUSE, fluid and imaging biomarkers, along with clinical manifestations, were used to classify patients as MSA or Parkinson’s Disease/Dementia with Lewy Bodies. Patients who tested negative for alpha-synuclein were excluded from the analyses. In the trial, novel MRI imaging techniques and deep learning segmentation were used to assess brain volume across brain Regions of Interest relevant to MSA. Structural MRI plays a critical role in both diagnosing MSA and monitoring disease progression. Subcortical brain volume shows potential as a biomarker for evaluating disease-modifying therapies. Over the course of one year, MRI with deep-learning segmentation revealed significant brain volume reduction in MSA ROIs whereas the PD patients showed no significant brain volume changes. In contrast, the MSA patients exhibited significant volume reductions in the cerebellum, globus pallidus, and brainstem. In addition, the MSA-P patients showed significant volume loss in the putamen. The results illustrate the correlation between the brain volume reduction and worsening clinical scores, as measured by the UMSARS, providing a visual representation of disease progression. Title: Effects of ATH434, a Clinical-Phase Small Molecule with Moderate Affinity for Iron, in a Parkinson’s Disease Model in Macaques: Results: The presentation demonstrated that ATH434 treatment led to lower iron levels in the affected area of the brain, the substantia nigra, and improved motor performance and general function in monkeys with experimentally induced Parkinson’s disease. At week 12, all 5 ATH434-treated macaques had stable or improving scores from Baseline while two of three vehicle-treated macaques did not demonstrate improvement. The improved general behavior was well-correlated with reduced motor impairment. These favorable parkinsonian outcomes observed in each of the ATH434-treated monkeys were also associated with increased levels of striatal synaptophysin, a protein marker that reflects functional connections between neurons, suggesting functional recovery of nerve endings in this critical motor pathway. These results support further investigation of ATH434 for the treatment of Parkinson’s disease.