Alterity Therapeutics (ATH) Study Update summary

Clinical development overview

• ATH434 is being developed for multiple system atrophy (MSA), a rare, rapidly progressive neurodegenerative disorder with no approved treatments.

• The program includes a completed natural history study (BioMUSE), an ongoing double-blind phase 2 trial (201), and an open-label biomarker study (202) in more advanced patients.

• MSA and Parkinson's disease share similar pathological features, including iron accumulation and alpha-synuclein aggregation.

• The therapeutic strategy targets excess labile iron and alpha-synuclein to reduce oxidative stress and neuronal death.

ATH434-202 open-label study results

• Interim data from 7 patients after 6 months of treatment showed 43% had improvement in daily living activities (UMSARS), which is notable given the typical rapid decline in MSA.

• 29% of patients reported stable or improved neurological symptoms on the Global Impression of Change scale.

• No serious adverse events attributed to ATH434; the drug was well tolerated with no new safety signals.

• Biomarker analysis showed stable brain volume and iron levels in clinical responders, with smaller increases in myo-inositol and stable neurofilament light chain (NFL) levels, supporting clinical findings.

• Patients with less advanced disease showed better outcomes, supporting the focus on early-stage patients in the double-blind trial.

Regulatory and future development considerations

• The primary endpoint for the double-blind trial is change in brain iron, with UMSARS as a key secondary endpoint; endpoints may be adjusted based on ongoing data review.

• FDA prioritizes functional outcomes (UMSARS) over biomarker changes for approval, emphasizing patient benefit.

• No prior phase 2 or 3 trials in MSA have shown robust positive effects on UMSARS; the disease's heterogeneity makes comprehensive assessment important.

• ATH434 may have potential for use in Parkinson's disease and could be combined with other therapies targeting different disease mechanisms.

• The program is fully funded through the upcoming double-blind trial readout, with ongoing interest from partners and potential for additional funding from organizations like the Michael J. Fox Foundation.