Full Press Release Details
Appendix 4C - Q1 FY25 Quarterly
MELBOURNE, AUSTRALIA AND SAN FRANCISCO,
USA - 31 October 2024: Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) ("Alterity" or "the Company"),
a biotechnology company dedicated to developing disease modifying treatments for neurodegenerative diseases, today released its Appendix
4C Quarterly Cash Flow Report and update on company activities for the quarter ending 30 September 2024 (Q1 FY25).
"We are excited about what
this fiscal year has to offer as we started by reporting promising data from our Phase 2 clinical trial in participants with advanced
multiple system atrophy (MSA)," said, David Stamler, M.D., Chief Executive Officer of Alterity. "The interim results from
the ATH434-202 study suggest that ATH434 has potential to modify disease progression. Importantly, the stabilization of iron content in
certain brain regions, combined with key biomarker data, indicates that ATH434 may slow neurodegeneration by modulating brain iron levels
and reducing oxidative injury. These early data are an exciting indicator of what we might expect to see from our ATH434-201 trial in
MSA patients with early-stage disease that is expected to read out in January 2025."
"Last month, we delivered
multiple presentations at the International Congress of Parkinson's Disease and Movement Disorders (MDS), a prominent
neurology meeting. At this event, we presented clinical and preclinical data demonstrating the potential of ATH434 in a variety of neurological
conditions including early-stage MSA, advanced MSA, and Parkinson's disease. We look forward to presenting additional data at medical
meetings, and the topline results from both our ATH434-201 and ATH434-202 trials in calendar year 2025," added, Dr. Stamler.
Alterity's cash position
on 30 September 2024 was A$9.28 with operating cash outflows for the quarter of A$3.31M.
In accordance with ASX Listing Rule
4.7C, payments of A$94k made to related parties and their associates included in item 6.1 of the Appendix 4C incorporates directors'
fees, consulting fees, remuneration and superannuation at commercial rates.
Operational Activities
ATH434-202: Open-label, Biomarker Phase 2 Clinical
Trial in Advanced MSA
On 17 July 2024, Alterity
reported positive interim data from the ATH434-202 trial in participants with advanced MSA. The data were also presented in September
2024 as both a late-breaking oral presentation and poster session by Daniel O. Claassen, M.D., M.S., Professor of Neurology, Vanderbilt
University Medical Center at the International Congress of Parkinson's Disease and Movement Disorders (MDS). The
early outcomes reported from the interim analysis suggest that ATH434 has potential to modify disease progression.
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. ATH434 was well tolerated with no drug-related serious adverse events, and most adverse events were mild to moderate, showing
a favorable safety profile.
The data suggest that ATH434 may
have a disease-modifying effect in MSA, as 30% of participants had stable or improved clinical outcomes (clinical responders). The average
change in Unified MSA Rating Scale Part I (UMSARS I) scores over 6 months was smaller than observed in a historical group of untreated
MSA patients, suggesting reduced disability on activities of daily living.
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, the clinical responders on average showed stability in iron levels on MRI in the substantia nigra, putamen and globus pallidus,
as well as stable levels of Neurofilament light chain (NfL), a marker of axonal injury, when compared to participants who declined. 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.
The trial remains ongoing with Topline 12-month
results expected in the first half of calendar year 2025.
ATH434-201: Randomized, Double-Blind Phase 2 Clinical
Trial in Early-State MSA
In September 2024, Dr.
Stamler delivered an Oral Platform presentation and poster session at MDS, entitled, "A Phase 2 Study of ATH434, a Novel
Inhibitor of -Synuclein Aggregation, for the Treatment of Multiple System Atrophy". The oral presentation and poster
described 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 they had early-stage (clinically probable) MSA.
The presentation further demonstrated
that increased iron levels were evident in multiple subcortical brain regions, with increases being observed in the substantia nigra in
nearly all subjects, and that ATH434 has potential to slow neurodegeneration based on its ability to redistribute this excess brain iron.
Data were also presented indicating that plasma levels of neurofilament light chain, a marker of neuronal injury, were correlated with
disease severity at baseline.
The trial remains on track to complete
in November 2024. The data from the trial will then be analyzed and the Company expects to report topline results in January 2025.
bioMUSE Natural History Study
The Company's "Biomarkers
of progression in Multiple System Atrophy" (bioMUSE) natural history study continues to produce promising data to track the progression
of individuals with MSA and characterize MSA in terms of various biomarkers. At the MDS meeting in September 2024, a poster featuring
bioMUSE data was presented entitled, "Association Between Clinical Progression in Multiple System Atrophy and Brain Volume Changes
Evaluated via Deep Learning Segmentation". The poster described the novel MRI imaging techniques and deep learning segmentation
that were used to assess brain volume in MSA brain regions of interest (ROI) in bioMUSE participants. 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 Parkinson's disease 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, patients with the parkinsonian variant of MSA 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 the basis for subcortical
brain volume as a potential biomarker in treatment studies.
ATH434 for the Treatment of Parkinson's
In September 2024, a
poster was presented at MDS entitled, "Effects of ATH434, a Clinical-Phase Small Molecule with Moderate Affinity for Iron, in
Hemiparkinsonian Macaques". 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.
Corporate Activities
On September 30, 2024, Alterity
announced Abby Macnish Niven as the Company's Chief Financial Officer. Ms Macnish Niven consults for a range of listed and unlisted
companies in governance, finance and corporate structure. She holds Bachelor of Commerce and Bachelor of Science degrees from University
of Western Australia and is a Chartered Finance Analyst.
During the quarter, management
participated in multiple investor activities including a webinar hosted by MST Financial, and a presentation hosted by ShareCafe.
About Alterity Therapeutics Limited
Alterity Therapeutics is a clinical
stage biotechnology company dedicated to creating an alternate future for people living with neurodegenerative diseases. The Company's
lead asset, ATH434, has the potential to treat various Parkinsonian disorders and is currently being evaluated in two Phase 2 clinical
trials in Multiple System Atrophy. Alterity also has a broad drug discovery platform generating patentable chemical compounds to treat