Full Press Release Details
Appendix 4C - Q2 FY25 Quarterly Cash Flow
MELBOURNE, AUSTRALIA AND SAN FRANCISCO, USA
- 24 January 2025: 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 31 December 2024 (Q2 FY25).
"The second fiscal quarter of this year
was extremely productive for Alterity and highlighted the tremendous potential of our lead asset, ATH434, as a promising therapy to treat
a variety of neurodegenerative diseases," said, David Stamler, M.D., Chief Executive Officer of Alterity. "Most significantly,
we completed the ATH434-201 study, our 12-month, double-blind Phase 2 clinical trial of ATH434 in early-stage Multiple System Atrophy
(MSA). Throughout the course of the trial, we have had tremendous interest from our clinical sites, doctors and patients around the globe
as we seek a treatment to slow the progression of this devastating condition. The data analysis is being finalized, and we remain on track
to report topline results in by early February."
"During the quarter, we delivered numerous
posters, presentations and publications on the potential of ATH434 as a disease modifying treatment in a variety of indications including
MSA, Parkinson's disease, and Friedreich's Ataxia. New, non-clinical data was presented that further describes the neuroprotective
qualities and the mechanism of action of ATH434 including the importance of iron and iron-targeting agents like ATH434 to treat neurodegenerative
diseases. Notably, positive clinical and biomarker interim results were presented from the ATH434-202 Phase 2 trial in advanced MSA, suggesting
that ATH434 has the potential to modify disease progression. The topline 12-month results from the 202 trial are expected in the first
half of calendar year 2025," concluded Dr. Stamler.
Alterity's cash position on 31 December
2024 was A$4.54M with operating cash outflows for the quarter of A$5.06M.
In accordance with ASX Listing Rule 4.7C, payments
of A$126K 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
ATH434-201: Randomized, Double-Blind
Phase 2 Clinical Trial in Early-State MSA
On 4 December 2024, Alterity reported the completion
of the ATH434-201 study as the last patient finished all clinical evaluations. The completion of the trial represented a major accomplishment
for Alterity in this rare neurodegenerative disease. With the achievement of this milestone, topline results remain on track to be reported
by early February 2025.
In October 2024, Alterity announced Dr. Stamler
delivered an Oral Platform presentation and poster session at the International Congress of Parkinson's Disease and Movement Disorders
(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 MSA. The presentation characterized the distribution
of iron in MSA affected brain areas and demonstrated that plasma levels of neurofilament light chain, a marker of neuronal injury, were
correlated with disease severity at baseline.
ATH434-202: Open-label, Biomarker Phase
2 Clinical Trial in Advanced MSA
In October 2024, Alterity announced the presentation
of positive interim data from the ATH434-202 trial as both a late-breaking oral presentation and poster session entitled, "Preliminary
Efficacy and Safety of ATH434 in Multiple System Atrophy", by Daniel O. Claassen, M.D., M.S., Professor of Neurology, Vanderbilt
University Medical Center at the MDS meeting. 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). Disease progression over 6 months was slower compared to a historical
group of untreated MSA patients, as indicated by the Unified MSA Rating Scale (UMSARS) Part I which assesses functional performance. The
clinical responders had stable brain iron and brain volume after 12 months treatment. The stabilization of iron content in MSA affected
brain regions, combined with stable levels of NfL, 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.
bioMUSE Natural History Study
The Company's "Biomarkers of progression
in Multiple System Atrophy" (bioMUSE) natural history study has produced promising data to track the progression of individuals
with MSA and characterize MSA in terms of various biomarkers.
In November 2024, data was presented at the 35th
International Symposium on the Autonomic Nervous System that highlighted Alterity's work to better understand not only how MSA initially
presents, but also how it progresses over time. The platform presentation entitled, "The MSA Atrophy Index: A Marker of Clinical
Progression in Multiple System Atrophy", was presented by Paula Trujillo Diaz, PhD, Research Assistant Professor, Department of
Neurology, Vanderbilt University Medical Center. The presentation described the use of state-of-the-art technology that goes beyond traditional
MRI methods to track the change in volume in specific regions of the brain affected in patients with MSA. Importantly, it was observed
that significant reductions in brain volume over 12 months correlated with clinical worsening of the disease. The results underscore the
importance of utilizing advanced neuroimaging and analytical methods in evaluating MSA which Alterity has implemented in its Phase 2 clinical
In October 2024, Alterity announced that a poster
featuring bioMUSE data was presented at the MDS meeting 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. 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.
Peer-reviewed Publication Describing Novel
Mechanism of Action for ATH434
In November 2024, the peer-reviewed journal, Metallomics,
published data on the importance of iron and iron-targeting agents like ATH434 to treat neurodegenerative diseases. The publication, entitled,
"ATH434, a promising iron-targeting compound for treating iron regulation disorders" was led by author Ashley Pall, Department
of Pharmaceutical Sciences at Wayne State University. This publication demonstrates the novel way in which ATH434 targets the labile,
or reactive, form of iron which can be so damaging to cells when in excess. The iron binding properties of ATH434 presented in the publication
support the characterization of ATH434 as an iron chaperone. The publication describes how ATH434 targets the toxic form of iron that
drives the pathology of a rare neurodegenerative disease known as Friedreich's Ataxia. This toxic form of iron is also involved
in the pathogenesis of Parkinson's disease and MSA.
Non-Clinical Data Describing Neuroprotection
In October 2024 promising new data related to
ATH434 were presented at the Society for Neuroscience 2024 that further the understanding of ATH434's potential as a disease modifying
treatment for neurodegenerative diseases, including Parkinson's disease and related disorders. The poster presentation entitled,
"Potent Antioxidant and Mitochondrial-protectant Effects of ATH434, a Novel Inhibitor of -Synuclein Aggregation with Moderate
Iron-binding Affinity," demonstrated that the neuroprotective and mitochondrial protectant properties of ATH434 include reducing
lipid damage in two distinct and disease-relevant neuronal injury models. ATH434's antioxidant properties were distinguished from
those of another iron binding agent approved for treating iron overload. This is key as oxidative injury is an important contributor to
the pathology of neurodegeneration. By addressing this injury in two different ways, both directly and by redistributing excess labile
iron, ATH434 has excellent potential to treat this group of diseases. The ability of ATH434 to reduce damage to lipid membranes undergoing
oxidative stress may augment its ability to slow disease progression. The study was run under the direction of Dr. Daniel J. Kosman, Distinguished
Professor of Biochemistry at the State University of New York at Buffalo.
ATH434 for the Treatment of Parkinson's
Also announced in October 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