Ann: Alterity Presents Encouraging New Phase 2 Data in MSA, page-6

Summary of the Announcement

Alterity Therapeutics presented new and encouraging data from its Phase 2 clinical trial of ATH434 for Multiple System Atrophy (MSA) at the 2025 American Academy of Neurology Annual Meeting.
Key outcomes from the study:

• Clinically meaningful efficacy observed in multiple assessments including:
  • UMSARS I (functional daily living scale)
  • Clinical Global Impression of Severity (CGI-S)
  • Orthostatic Hypotension Symptom Assessment
  • Increased outpatient physical activity measured by wearable sensors
• Target engagement confirmed: ATH434 reduced iron accumulation in MSA-affected brain regions—a hallmark of disease pathology.
• 50 mg dose showed a 48% reduction in disease progression vs. placebo (p=0.02).
• 75 mg dose showed a 30% reduction, indicating dose responsiveness.

Wearable sensor data from the bioMUSE study supported these findings and showed strong correlations between sensor activity and clinical function, using machine learning models for further validation.
Positives for ATH

1. Strong Clinical Efficacy
   • Demonstrated meaningful reduction in disease progression at 50 mg dose (48% improvement over placebo).
   • Positive trends in multiple domains, including motor performance and daily function.
2. Target Engagement Validated
   • Imaging confirmed reduction in iron in critical brain regions, supporting the drug’s mechanism of action.
3. Wearable Sensor Support
   • Real-world physical activity improvements reinforce clinical data.
   • Demonstrated effectiveness outside the clinic, providing real-world validation.
4. Orphan Drug Designation (US & EU)
   • Provides regulatory incentives including market exclusivity and potential for expedited approval.
5. No current disease-modifying treatments for MSA
   • High unmet need increases the value of a successful therapy.
   • First-mover advantage if ATH434 progresses to market.
6. Broad Platform Potential
   • ATH434 also has potential applications in Parkinson’s disease and other synucleinopathies.
   • Broader pipeline opportunities beyond MSA.
7. Strong Collaborations & Academic Partnerships
   • Vanderbilt University and BioSensics enhance scientific credibility and data quality.

Potential Upsides for Investors

• Breakthrough Therapy Potential: If further trials confirm results, ATH434 could be a blockbuster orphan drug.
• Market Catalyst: Positive FDA engagement could lead to fast-track status or Phase 3 initiation.
• Acquisition Target: Success in MSA and Parkinson’s could attract interest from big pharma.
• Valuation Growth: Current market cap is low compared to potential peak sales if approved.
• Multiple Milestone Events Ahead: Ongoing advanced-stage MSA trials, regulatory discussions, and potential licensing deals.