Full Press Release Details
Appendix 4C - Q4 FY25 Quarterly Cash Flow
MELBOURNE, AUSTRALIA AND SAN FRANCISCO, USA - 30 July
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 30 June 2025 (Q4 FY25).
"U.S. FDA Fast Track designation
for ATH434 in MSA was the highlight of the recent quarter that also featured additional positive clinical data from our Phase 2 double-blind
trial," said David Stamler, M.D., Chief Executive Officer of Alterity. "Receiving Fast Track Designation alongside the Orphan
Drug Designation we have already received underscores the promise of this potentially disease modifying therapy to address the urgent
needs of individuals with MSA. In addition, we presented additional efficacy data from the ATH434-201 double-blind trial at prominent
medical meetings, including slowing of disease progression on the Unified MSA rating scale or UMSARS, improvement in key symptoms of MSA,
and preserved activity in the outpatient setting."
"We were also very pleased
to announce positive results from our ATH434-202 open-label Phase 2 clinical trial this week, in which ATH434 demonstrated a clinical
benefit on the UMSARS and global assessments of neurological symptoms. Neuroimaging biomarkers showed target engagement and slowed brain
atrophy in a manner consistent with the double-blind study findings. Importantly, ATH434 continues to demonstrate a favorable safety profile.
These data reinforce our confidence in the MSA program as we prepare for interactions with the U.S. FDA," concluded Dr. Stamler.
Alterity's cash position
on 30 June 2025 was A$40.66M with operating cash outflows for the quarter of A$2.35M. In accordance with ASX Listing Rule 4.7C, payments
of A$119k 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
U.S. FDA Fast Track Designation for ATH434
In May 2025, the U.S. Food and
Drug Administration (FDA) granted Fast Track designation for ATH434 for the treatment of MSA. This designation is intended to accelerate
the development and review of novel investigational products such as ATH434 and recognizes its potential as an innovative approach to
address the high unmet need for treating MSA, a disease with no approved therapy. Fast Track designation for a drug candidate confers
some or all of the following benefits: opportunities for more frequent and early communication with the FDA throughout the development
process; rolling review for the future New Drug Application; and eligibility for Accelerated Approval and Priority Review, if relevant
Fast Track eligibility requires
demonstration of the potential for clinically meaningful benefits, which can include the mechanism of action, preclinical studies, or
data from patient studies. Alterity's previous interactions with the FDA indicated that the modified Unified Multiple System Atrophy
Rating Scale Part I (UMSARS I)1 scale is considered a clinically meaningful endpoint for MSA. Alterity's Fast Track application
included top-line data from the ATH434-201 randomized, double-blind, placebo-controlled Phase 2 clinical trial which demonstrated efficacy
on the modified UMSARS I in addition to preclinical data confirming that ATH434 is a moderate affinity iron chaperone and showed efficacy
in animal models of MSA.
ATH434-201: Randomized, Double-Blind,
Placebo Controlled Phase 2 Clinical Trial in MSA
In May 2025 additional analyses
from the ATH434-201 trial were presented at the International MSA Congress. The presentation, entitled, "ATH434 Slowed Disease Progression
in a Phase 2 Study in Multiple System Atrophy", evaluated the clinical analysis population (n=71) who had at least one post-baseline
assessment of the key clinical endpoint, the modified UMSARS I activities of daily living scale. On this endpoint, ATH434 demonstrated
a clinically significant reduction in disease severity versus placebo, with a 48% relative treatment effect at the 50 mg dose (p=0.02)^
and a 30% relative treatment effect at the 75 mg dose at 52 weeks.
Additional efficacy assessments
showed improvement consistent with the UMSARS I findings. The Clinical Global Impression of Severity Scale2 demonstrated improvement
compared to placebo at both dose levels, with difference at 50 mg achieving nominal statistical significance (p=0.0088). On the Orthostatic
Hypotension Symptom Assessment (a patient reported outcome), on average, placebo patients worsened by approximately 6 points over 52 weeks
whereas both ATH434 treatment groups improved over the same period. Baseline differences in disease severity likely explain the different
responses in 50 mg and 75 mg treatment groups.
Increased activity in the outpatient
setting, as measured by wearable movement sensors, was observed at both dose levels as compared to placebo utilized in the trial, with
clinically meaningful improvements in step count, bouts of walking, total walking time, and total standing time. ATH434 was well tolerated
with similar adverse event rates compared to placebo and no serious or severe adverse events attributed to ATH434. Regarding neuroimaging
data in 61 participants, ATH434 demonstrated target engagement by stabilizing or reducing iron accumulation at both dose levels compared
to placebo in MSA affected brain regions. In addition, ATH434 demonstrated trends in reducing brain atrophy at both dose levels compared
to placebo. Overall, the study results support continued advancement of ATH434 for the treatment of MSA.
During the period, multiple additional
presentations were delivered on the positive results from the ATH434-201 trial:
ATH434-202: Open-label, Biomarker
Phase 2 Clinical Trial in Advanced MSA
Subsequent to the period end,
on 28 July 2025, Alterity announced positive positive topline data from the ATH434-202 open-label Phase 2 clinical trial in individuals
with MSA. Ten (10) participants were enrolled and were treated with oral ATH434 75 mg twice daily for 12 months. The study assessed the
safety and efficacy of ATH434 treatment on clinical and biomarker endpoints and evaluated a patient population with more advanced disease
than was studied in the double-blind Phase 2 trial. The topline data showed that ATH434 conferred a clinical benefit on areas of impairment
in MSA and stabilized key biomarkers that underpin the pathology of the disease.
ATH434 demonstrated a benefit
on the key clinical endpoint UMSARS I, which increased from baseline to 12 months by 3.5 (4.7) points. These study data compare favorably
to historical data in a similar MSA population, where an increase of 6.5 (6.0) points over 12 months was observed.3 Regarding
overall neurological symptoms, 30% (3/10) of participants stabilized or improved on both the Clinical Global Impression of Change (CGIC)4
and the Patient Global Impression of Change (PGIC)5 scales. On the important symptom of orthostatic hypotension6,
low blood pressure symptoms stabilized on average in study participants over the treatment period. The aggregate data indicate that ATH434
has similar efficacy in this advanced MSA population as was observed in the earlier stage patients in the ATH434-201 trial.
The key biomarker endpoint was
defined as the change in brain volume from baseline to 12- months, as measured by the MSA Atrophy Index (MSA-AI)7. Neuroimaging
outcomes indicate that ATH434 slowed brain atrophy in MSA affected areas when compared to placebo-treated participants in Study 201. Moreover,
the effects on brain volume were comparable to those observed in participants in the 75 mg dose group in Study 201. In addition, ATH434
led to lower iron accumulation in the putamen and globus pallidus as compared to placebo treated patients in Study 201, providing further
evidence of target engagement. On average, plasma and CSF Neurofilament Light Chain (NfL) levels were stable over the 12-month treatment
ATH434 was well-tolerated with
a favorable safety profile. No serious adverse events (SAEs) related to ATH434 were reported, and most adverse events were mild to moderate
bioMUSE Natural History Study
Subsequent to the period end,
on 24 July 2025, the Company announced that an innovative neuroimaging measure developed in Alterity's Biomarkers of Progression
in Multiple System Atrophy (bioMUSE) Natural History Study was featured in the peer-reviewed journal Annals of Clinical and Translational
Neurology. The publication, entitled "The MSA Atrophy Index (MSA-AI): An Imaging Marker for Diagnosis and Clinical Progression
in Multiple System Atrophy," describes how deep learning methods, a form of artificial intelligence, were used to precisely define
the neuroanatomy of key brain regions along with development of a novel brain atrophy measure for tracking disease progression in MSA
patients over one year. The results were then correlated with clinical measures of disease severity over the same timeframe. Development
of the MSA Atrophy Index can enhance the understanding of MSA progression and provide support for using brain atrophy markers for the
evaluation of disease-modifying therapies. These tools offer potential applications in diagnosis, staging, and monitoring of disease severity,
contributing to more personalized care in MSA.
In May 2025, additional presentations were delivered from
bioMUSE at the at the International MSA Congress in May:
Corporate Activities
During the period, Alterity strengthened its
balance sheet with a total of A$26.3M raised in gross proceeds upon completion of the second tranche of a two-tranche placement.
During the period, Alterity also received a refund of A$3.98M from the Australian Taxation Office under the Australian
Government's Research and Development Tax Incentive (R&DTI) Scheme for eligible activities conducted during the financial