Anavex Life Sciences (AVXL) 44th Annual J.P. Morgan Healthcare Conference summary

Strategic vision and therapeutic approach

• Focus on upstream intervention in CNS diseases by restoring autophagy, aiming for patient-oriented, personalized medicine in neurodegeneration.

• Lead asset blarcamesine is a once-daily oral small molecule targeting sigma-1 activation to restore cellular homeostasis, with potential for broad CNS applications.

• Emphasis on convenience and patient preference for oral therapies, reducing the need for hospital visits and improving quality of life.

• Financially stable with over three years of cash, no debt, and strong IP protection through 2040.

• Non-dilutive funding from foundations supports a fiscally conservative approach.

Clinical data and efficacy

• Phase IIb/III trial of blarcamesine showed significant slowing of cognitive decline, with up to 49.8% benefit in pre-specified populations at 48 weeks.

• Demonstrated strong safety profile, no neuroimaging adverse events, and no deaths in trials.

• Biomarkers such as brain volume loss and Aβ42 plasma ratio showed significant improvement.

• Long-term extension study indicated up to 18 months of sustained patient benefit in maintaining independence.

• Quality of life measures improved above baseline for key genetic groups after 48 weeks.

Mechanism of action and precision medicine

• Blarcamesine activates sigma-1 receptors, restoring autophagy and reducing cellular stress, confirmed in vivo and in vitro.

• Stronger clinical response observed in patients with wild-type sigma-1 gene, representing about 70% of the population.

• Combination of wild-type sigma-1 and COL24A1 genes led to 84.7% clinical benefit over placebo, approaching normal aging cognitive profiles.

• Mechanism validated by PET studies and peer-reviewed publications.