Appendix 4C – Q4 FY24 Quarterly Cash Flow Report

Rhea-AI Summary

Alterity Therapeutics (NASDAQ: ATHE) released its Q4 FY24 Quarterly Cash Flow Report, highlighting positive interim data from the ATH434-202 Phase 2 clinical trial for Multiple System Atrophy (MSA). The trial showed improvement in daily living activities and stable or improved neurological symptoms in some patients. The bioMUSE Natural History Study continues to inform Alterity's Phase 2 trials, characterizing early-stage MSA.

Key points:

• Cash balance of A$12.6M as of June 30, 2024
• Positive interim data from ATH434-202 Phase 2 trial
• Ongoing ATH434-201 Phase 2 trial for early-stage MSA
• Presentations at World Orphan Drug Congress and American Academy of Neurology Annual Meeting
• Promising results from bioMUSE study guiding patient selection and endpoints for Phase 2 trials

Positive

• Positive interim data from ATH434-202 Phase 2 trial showing improvement in daily living activities and neurological symptoms
• Independent Data Monitoring Committee recommended continuation of ATH434-201 Phase 2 study without modification
• bioMUSE Natural History Study providing valuable data to inform patient selection and endpoints for Phase 2 trials
• Promising results in Parkinson's Disease animal model showing reduced Parkinsonism and improved motor skills

Negative

• Operating cash outflows of A$5.6M for the quarter
• Cash balance of A$12.6M as of June 30, 2024, potentially limiting future operations without additional funding

Financial Analyst

Alterity Therapeutics' Q4 FY24 report reveals a cash balance of A$12.6 million as of June 30, 2024, with quarterly operating cash outflows of A$5.6 million. This financial position, while not critically low, suggests a need for careful cash management in the coming quarters. The burn rate indicates that without additional funding, the company may face financial constraints within the next 6-8 quarters, depending on the intensity of their clinical trial activities.

The company's focus on ATH434, their lead candidate for Multiple System Atrophy (MSA), is progressing through multiple Phase 2 trials. The positive interim data from the ATH434-202 trial and the insights gained from the bioMUSE study are encouraging, potentially increasing the asset's value. However, it's important to note that Phase 2 trials are still early-stage and success here doesn't guarantee ultimate FDA approval or commercial viability.

Investors should closely monitor the company's cash position and potential need for additional financing, which could lead to dilution. The upcoming topline results from the ATH434-201 trial, expected by January 2025, will be a critical milestone that could significantly impact the company's valuation and future funding prospects.

Medical Research Analyst

The interim data from Alterity's ATH434-202 Phase 2 trial in advanced MSA patients is promising, with 43% of participants showing improvement on the UMSARS Activities of Daily Living Scale after 6 months of treatment. Additionally, 29% of participants demonstrated stable or improved neurological symptoms. These results, while preliminary, suggest potential efficacy of ATH434 in modifying disease progression.

The bioMUSE Natural History Study has provided valuable insights into early-stage MSA progression, particularly regarding brain iron accumulation and volume changes. The statistically significant increase in iron in the substantia nigra and decrease in brain volume in affected regions over 12 months offer potential biomarkers for disease progression and treatment efficacy.

The correlation between plasma Neurofilament Light Chain (NfL) levels and disease severity in MSA patients is a significant finding. If validated in larger studies, NfL could serve as a valuable biomarker for monitoring disease progression and treatment response in clinical trials.

While these results are encouraging, it's important to remember that Phase 2 trials are primarily designed to assess safety and gather preliminary efficacy data. The true test of ATH434's potential will come in larger, randomized Phase 3 trials. Investors should remain cautiously optimistic as the drug progresses through the development pipeline.

Biotechnology Industry Analyst

Alterity Therapeutics is making significant strides in the challenging field of neurodegenerative diseases, particularly Multiple System Atrophy (MSA). Their lead candidate, ATH434, is showing promise in both early and advanced MSA patients, which is noteworthy given the lack of effective treatments for this condition.

The company's approach of targeting iron accumulation in the brain is innovative and supported by their preclinical and early clinical data. The positive results from the monkey model of Parkinson's disease further validate this approach and suggest potential applications beyond MSA.

Alterity's use of advanced imaging techniques and machine learning in the bioMUSE study demonstrates a sophisticated approach to drug development. This could potentially streamline future clinical trials and improve patient selection, ultimately increasing the chances of successful outcomes.

However, investors should be aware that the neurodegenerative disease space is notoriously difficult, with many promising candidates failing in late-stage trials. The company's focus on rare diseases like MSA could be a double-edged sword - while it may face less competition, the market size is also

The upcoming topline results from the ATH434-201 trial in early 2025 will be a important inflection point for the company. Positive results could attract partnership interest from larger pharmaceutical companies, while negative results could significantly impact the company's prospects and valuation.

Highlights

• Positive interim data reported from ATH434-202 Phase 2 clinical trial showing improvement on the UMSARS Activities of Daily Living Scale and stable or improved neurological symptoms in some patients
• Data from the bioMUSE Natural History Study continues to characterize early stage MSA and inform Alterity’s Phase 2 clinical trials
• Multiple data presentations at the World Orphan Drug Congress and the American Academy of Neurology (AAN) Annual Meeting
• Cash balance on 30 June 2024 of A$12.6M

MELBOURNE, Australia and SAN FRANCISCO, July 31, 2024 (GLOBE NEWSWIRE) -- 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 2024 (Q4 FY24).

“We have made great strides over the last two months with the positive interim data readout from our ATH434-202 Phase 2 clinical trial and the important observations from our bioMUSE Natural History Study that continue to guide development of ATH434,” said David Stamler, M.D., Chief Executive Officer of Alterity. “I am very encouraged by the results from our 202 study in patients with advanced Multiple System Atrophy (MSA) where we saw favorable clinical and biomarker outcomes in some patients suggesting that ATH434 has the potential to modify the course of this devastating condition. We were also very pleased to see that the clinical responders had biomarker evidence of stable disease as this provides an objective indication of potential efficacy.”

“Our bioMUSE study continues to provide valuable information to inform our patient selection criteria and choose endpoints for our Phase 2 clinical trials. This observational study has allowed us to monitor the progression of MSA in earlier stage patients and further characterize this devastating disease. Working with our colleagues at Vanderbilt University, we have employed novel MRI technology and machine learning to precisely analyze brain iron content and brain volumes in these patients over time. The results from the study have guided us to modify our endpoints in the ATH434-202 study. The data from our 202 and bioMUSE studies increases my overall confidence in the ATH434 development program,” concluded Dr. Stamler.

Alterity’s cash position on 30 June 2024 was A$12.6M with operating cash outflows for the quarter of A$5.6M.

In accordance with ASX Listing Rule 4.7C, payments 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 8 May 2024, Alterity announced that an independent Data Monitoring Committee (DMC) completed its third prespecified review of unblinded clinical trial data from the ATH434-201 Phase 2 study. The DMC expressed no concerns about safety and recommended that the study continue as planned without modification. This recommendation is an important milestone as participants are able to safely tolerate ATH434 as their time on study increases.

In April 2024, important new data on ATH434 was presented at the World Orphan Drug Congress in a poster presentation, entitled, “Biophysical Characteristics of ATH434, a Unique Iron-Targeting Drug for Treating Friedreich’s Ataxia.” The study evaluated the ability of ATH434 to target the toxic form of iron that drives the pathology of Friedreich’s Ataxia, a rare neurodegenerative disease that affects young children to young adults. The investigation provides important insights into the mechanism of action of ATH434, namely that it selectively targets the labile iron implicated in the pathology of important neurodegenerative diseases. In this way, ATH434 behaves like a chaperone to redistribute iron within the body.

In April 2024, a poster was presented at the American Academy of Neurology (AAN) 2024 Annual Meeting, entitled, “A Phase 2 Study of ATH434, a Novel Inhibitor of α-Synuclein Aggregation, for the Treatment of Multiple System Atrophy”. The poster described the baseline characteristics for the 65 evaluable participants from the ATH434-201 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. Overall, the participants had a mean duration of motor symptoms of two years. The data showed increased iron in areas of pathology and elevated plasma Neurofilament Light Chain (NfL) levels at baseline that correlated significantly with disease severity.

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 by January 2025.

ATH434–202: Open-label, Biomarker Phase 2 Clinical Trial in More Advanced MSA

Subsequent to the quarter end, on 17 July 2024, Alterity reported positive interim data from the ATH434-202 trial in participants with advanced MSA. 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 the global impression of change 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.

bioMUSE Natural History Study

On 30 May 2024 Alterity hosted a webinar to discuss data from the bioMUSE Natural History Study. The goal of the observational bioMUSE study is to optimize patient selection and choose endpoints for the Company’s Phase 2 clinical trials. This study enrolled 21 individuals who were observed for 12 months to characterize early-stage MSA in terms of various biomarkers. In particular, the focus is on brain iron, brain volume, and the pathology in glial support cells. Utilizing novel MRI technology, Alterity’s partners at Vanderbilt University have optimized specialized MRI methods, including machine learning (a form of artificial intelligence), to establish standardized methods to analyze brain iron and brain volumes with precision. Importantly, they developed a new, novel imaging biomarker to assess brain volume in MSA affected regions. The bioMUSE data showed a statistically significant increase in iron over 12 months in the substantia nigra, and statistically significant decreases in brain volume observed in affected regions at 12 months.

Also at AAN, a poster was presented at the AAN 2024 Annual Meeting, entitled, “Neurofilament Light Chain and Clinical Progression in Early Multiple System Atrophy”. The poster described results from bioMUSE in which changes in clinical severity of 15 patients across a span of 12 months were compared with plasma biomarkers with a goal of establishing meaningful correlations. Importantly, the observational data suggest the fluid biomarker NfL may be used as a marker of disease severity in studies of MSA as it holds promise for measuring the extent of disease, tracking its progression, and forecasting the onset of clinical manifestations associated with MSA.

ATH434 for the Treatment of Parkinson’s Disease

A poster was also presented at AAN entitled, “Effects of ATH434, a Clinical-Phase Small Molecule with Moderate Affinity for Iron, in Hemiparkinsonian Macaques”. The presentation showed that ATH434 can reduce Parkinsonism in a higher order animal, the monkey, with symptoms that closely parallel human disease. Importantly, the improvements in motor skills and general functioning that parallel human parkinsonism were associated with reductions in abnormal iron in affected brain regions. These favorable parkinsonian outcomes observed in 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. Taken together, the findings in this study increase the Company’s confidence in their approach in the ongoing Phase 2 program in MSA.

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 the underlying pathology of neurological diseases. The Company is based in Melbourne, Australia, and San Francisco, California, USA. For further information please visit the Company’s web site at www.alteritytherapeutics.com.

Authorisation & Additional information
This announcement was authorized by David Stamler, CEO of Alterity Therapeutics Limited.

Investor and Media Contacts:

Australia
Hannah Howlett
we-aualteritytherapeutics@we-worldwide.com
+61 450 648 064

U.S.
Remy Bernarda
remy.bernarda@iradvisory.com
+1 (415) 203-6386

Forward Looking Statements

This press release contains "forward-looking statements" within the meaning of section 27A of the Securities Act of 1933 and section 21E of the Securities Exchange Act of 1934. The Company has tried to identify such forward-looking statements by use of such words as "expects," "intends," "hopes," "anticipates," "believes," "could," "may," "evidences" and "estimates," and other similar expressions, but these words are not the exclusive means of identifying such statements.

Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are described in the sections titled “Risk Factors” in the Company’s filings with the SEC, including its most recent Annual Report on Form 20-F as well as reports on Form 6-K, including, but not limited to the following: statements relating to the Company's drug development program, including, but not limited to the initiation, progress and outcomes of clinical trials of the Company's drug development program, including, but not limited to, ATH434, and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to the difficulties or delays in financing, development, testing, regulatory approval, production and marketing of the Company’s drug components, including, but not limited to, ATH434, the ability of the Company to procure additional future sources of financing, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug compounds, including, but not limited to, ATH434, that could slow or prevent products coming to market, the uncertainty of obtaining patent protection for the Company's intellectual property or trade secrets, the uncertainty of successfully enforcing the Company’s patent rights and the uncertainty of the Company freedom to operate.

Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

FAQ

What were the key findings from Alterity's ATH434-202 Phase 2 clinical trial for MSA?

The ATH434-202 Phase 2 clinical trial showed improvement on the UMSARS Activities of Daily Living Scale and stable or improved neurological symptoms in some patients with Multiple System Atrophy (MSA). Clinical responders also showed reduced iron accumulation in brain regions and stable levels of NFL, a marker of axonal injury.

When is Alterity Therapeutics (ATHE) expected to report topline results for the ATH434-201 Phase 2 trial?

Alterity Therapeutics (ATHE) expects to report topline results for the ATH434-201 Phase 2 trial by January 2025. The trial is on track to complete in November 2024, after which the data will be analyzed.

What is the current cash position of Alterity Therapeutics (ATHE) as of June 30, 2024?

Alterity Therapeutics (ATHE) reported a cash balance of A$12.6 million as of June 30, 2024.

How is the bioMUSE Natural History Study contributing to Alterity's (ATHE) research on Multiple System Atrophy?

The bioMUSE Natural History Study is helping Alterity (ATHE) optimize patient selection and choose endpoints for Phase 2 clinical trials. It provides valuable data on early-stage MSA, including brain iron accumulation, brain volume changes, and biomarkers like Neurofilament Light Chain (NfL) that correlate with disease severity.