Alterity Therapeutics announced positive interim data from the ATH434-202 open-label Phase 2 clinical trial in patients with multiple system atrophy (MSA). ATH434 has been shown preclinically to reduce a-synuclein pathology and preserve neuronal function by restoring normal iron balance in the brain. The interim analysis included clinical and biomarker data on 7 participants treated with ATH434 for 6 months and neuroimaging data on 3 participants who were treated for 12 months.

After 6 months of treatment, 43% of participants showed improvement on the UMSARS1, indicating reduced disability on activities of daily living. Over the same period, 29% of participants had stable or improved neurological symptoms (clinical responders) as assessed by both the treating physician and the patient. Importantly, the clinical responders on average had reduced accumulation of iron on MRI in the substantia nigra, putamen and globus pallidus and stable levels of NFL, a marker of axonal injury, when compared to participants who declined.

ATH434-202 Interim Results A total of 10 participants have been enrolled in the trial. The interim data reported now is from the 7 patients who have completed six months of treatment with ATH434, 3 of whom have also completed 12 months of treatment. Only neuroimaging data are available from month 12.

The participants in the trial were diagnosed with MSA using a multimodal approach (clinical, neuroimaging, fluid biomarkers) and treated with oral ATH434 75 mg twice daily. Clinical, biomarker and safety assessments were conducted during the study. While the data are preliminary, the Company sees a positive trend with the current participant patient outcomes.

Clinical Assessments at Month 6 Unified MSA Rating Scale Part I, historical review (UMSARS) 43% (3/7) of participants had lower scores (improvement) on the UMSARS that assesses activities of daily living affected in MSA, such as speech, swallowing, walking and urinary/bowel function. In the trial, mean (SD) UMSARS scores (N=7) increased from baseline to 6 months by 1.7 (5.1) points. These study data compare favorably to historical data in a similar MSA population that demonstrated an increase of 3.9 (4.6) points over 6 months.2 Global Impression of Change 29% (2/7) of participants stabilized or improved on the Clinical Global Impression of Change (CGIC) scale, which asks the investigator to evaluate overall neurological symptoms as compared to immediately before starting therapy.

29% (2/7) of participants also stabilized or improved on the Patient Global Impression of Change (PGIC) scale which asks the patient to evaluate their overall neurological symptoms as compared to immediately before starting therapy. Safety In general, ATH434 was well tolerated by study participants and most adverse events were mild to moderate in severity. No serious adverse events related to study drug were reported.

Biomarker Assessments at Month 6 and Month 12 MRI Biomarkers (n=7): Brain Volume:   At Month 6, there were similar declines in brain volume, as assessed by the MSA-atrophy index (MSA-AI)3 in all participants consistent with the nature of MSA. However, in the clinical responders, brain volume assessed by the MSA-AI was stable between Month 6 and Month 12. Iron content in the substantia nigra was stable over 12 months in the clinical responders.

Myoinositol is an exploratory biomarker of glial cell pathology in MSA. Treatment with ATH434 led to smaller increases in myoinositol in clinical responders compared to participants who worsened. Fluid Biomarkers (n=5): Neurofilament Light Chain (NfL) is a marker of axonal injury in neurons and has been shown to correlate with disease severity in many neurological diseases.

In the trial, clinical responders had stable spinal fluid NfL levels on average whereas those who declined clinically had increased spinal fluid NfL levels.