Alterity Therapeutics Hits Milestone in Fight Against MSA with Promising Phase 2 Results
- Noel Ong
- May 16
- 5 min read
Alterity Therapeutics Limited (ASX: ATH, NASDAQ: ATHE) has unveiled compelling Phase 2 clinical trial data for its lead drug candidate, ATH434—a major advancement in treating Multiple System Atrophy (MSA). The findings were presented at the prestigious European MSA Symposium in London, drawing attention from global experts in neurodegenerative research.
What is MSA?
Alterity Therapeutics Limited is a rare, rapidly progressing neurological disorder affecting movement and involuntary functions. It involves:
Slowed movement, rigidity
Autonomic dysfunction (blood pressure, bladder control)
Progressive loss of coordination
Accumulation of α-synuclein in the brain
There are currently no approved treatments that slow disease progression.
ATH434 – A New Class of Treatment Targeting the Underlying Pathology
ATH434 is an oral iron chaperone designed to correct abnormal iron metabolism in the brain, a driver of oxidative stress and protein aggregation in MSA (Figure 1).
Figure 1: Excess labile iron and alpha-synuclein aggregation driving MSA pathology (Source: Alterity Phase 2
Presentation at MSA Symposium 2025)
How It Works:
ATH434 reduces the buildup of α-synuclein, a harmful protein linked to MSA. It cuts oxidative damage by up to 80%, helping protect brain cells. The drug has shown effectiveness in animal models of both MSA and Parkinson’s disease (Figure 2).
Figure 2: Development Approach: Address Underlying Pathology (Source: Alterity Phase 2 Presentation at MSA Symposium 2025)
The ATH434-201 trial enrolled 77 patients for 12-month treatment across three arms: placebo, 50 mg BID, and 75 mg BID. Assessments included motor function scales, patient-reported outcomes, MRI, and wearable sensor data.
Here’s what the trial revealed:
✅ Clinical Efficacy
50 mg dose: Achieved a 48% reduction in disease severity (p=0.02) using the UMSARS I scale.
75 mg dose: Showed a 30% reduction, though not statistically significant.
Clinical Global Impression of Severity scores also improved significantly at 50 mg (p=0.009).
✅ Patient-Reported Benefit
ATH434 users improved on symptoms of orthostatic hypotension, while placebo patients worsened by ~6 points.
Wearable sensor data showed increased daily activity, including walking and standing time, especially at 50 mg.
✅ Brain Imaging & Biomarkers
MRI scans confirmed that ATH434 stabilized or reduced iron accumulation in MSA-affected brain regions (Figure 3).
Trends in reduced brain atrophy were also observed, indicating potential neuroprotection (Figure 4).
Figure 3: Change in Iron Content by MRI (QSM) (Source: Alterity Phase 2 Presentation at MSA Symposium 2025)
Figure 4: ATH434 Demonstrated Trends in Reduced Brain Atrophy Change from Baseline in Brain Volume – MSA Atrophy Index^ (Source: Alterity Phase 2 Presentation at MSA Symposium 2025)
✅ Well-Tolerated/Safety Profile
Side effect profiles were similar across placebo and treatment groups.
No serious adverse events were linked to ATH434.
Why It Matters
These results position ATH434 as one of the most promising candidates in development for MSA. Not only does it demonstrate clinical benefits, but it also engages its target in the brain, a key benchmark for neurological drugs.
Alterity CEO Dr. David Stamler emphasized the significance:
“The strong clinical efficacy and novel mechanism of ATH434 was well received by leading experts. We’re motivated to continue advancing this therapy to improve the lives of individuals with MSA.”
With Orphan Drug Designation secured in the U.S. and Europe, Alterity is moving forward with an open-label Phase 2 biomarker study in more advanced MSA cases. The path to a potential breakthrough treatment is becoming clearer.
What’s Next for ATH434?
Second Phase 2 trial ongoing in advanced MSA
Orphan Drug Designation granted in U.S. & Europe
Broader potential for Parkinson’s disease and related disorders
Concluding Comments from Samso
The biotech sector is a new place for Samso, but as an investment, the principles are similar to the thinking process in mineral explorers. The steps to success are pretty much the same, but the commercialisation part may be faster and simpler for the biotech sector.
In terms of Alterity Therapeutics’ latest Phase 2 results, this stage marks a significant step forward in the treatment of Multiple System Atrophy. The success of the trials for ATH434, assuming that they continue to move in the right direction, will shape up to be a real game-changer in the fight against MSA.
For all those readers out there who can connect with what a medical solution to something like MSA, it's a bonus for the patient and the carers. The frustrating part is the time taken for distribution to be approved, and ultimately, the cost of the drug.
In terms of an investment option, I think that any successful drug trial that leads to being marketable will be a multi-bagger. The market capitalisation of the company is currently over AUD $100M.
Could this be one biotech story that could turn science into a serious impact? I am not well-versed enough to make that call. At this stage of Samso's journey into the biotech sector, this review is a way to educate Samso on the sector and increase our participation in the sector to bring more informed thoughts and understanding of the sector to the investing community.
Happy Investing
To support our independent nature of our work, please head over to our Support Page and give us a helping hand in any of the ways listed. This is a new initiate for the Samso Platform, and it was always the concept of Samso when we started this journey in 2018.
Disclaimer
The information or opinions provided herein do not constitute investment advice, an offer or solicitation to subscribe for, purchase or sell the investment product(s) mentioned herein. It does not take into consideration, nor have any regard to your specific investment objectives, financial situation, risk profile, tax position and particular, or unique needs and constraints.
Share to Grow: Your Bonus
Samso has just released an eBook: How to Add Value to your Share Portfolio
A lesson on geological models sought by mining companies that gives insight and an understanding of which portfolios are better - and potentially more lucrative – investments. Click here to download this eBook.
If you find this article informative and useful, please help me share the information. I try and write about topics that are interesting and have the potential to be of investment value. It is not easy to find stories that fit those parameters. If you or your organisation see the benefit of what Samso is trying to achieve and have a need to share your journey, please contact me at noel.ong@samso.com.au.
Samso is a trusted platform that equips dedicated investors with up-to-date industry knowledge and insights from top CEOs and thought leaders. By staying informed on business advancements and market trends, investors can enhance their financial decisions through a combination of expert guidance and their own research.
Comments