Voyager Therapeutics (VYGR) investor relations material

Pipeline catalysts

• Catalyst-rich period: tau antibody readout expected in Q4; first patient in the tau-knockdown gene therapy study expected in the coming months.

• FDA cleared the tau gene therapy program; Neurocrine plans to test a capsid in Friedreich’s ataxia, providing two clinical tests of blood-brain barrier-penetrant capsids.

• Gene therapy readouts: acute safety expected in Q1; CSF tau pharmacodynamics about a year after dosing starts; tau PET imaging later, with timing not yet set.

Tau evidence and biology

• CEO viewed BIIB080 as validating tau despite missing its CDR-SB dose-response primary endpoint; CSF tau fell 40% at the lowest dose and 50% at the highest, with little difference between doses.

• BIIB080 showed dose-related transient confusional states, which the CEO believes may have affected clinical endpoints; he attributed similar transient neurological effects with intrathecal ASOs to the modality, not tau.

• CEO said gene therapy studies in non-human primates showed tau reduction at 3 months and further knockdown at 6 months; he expects at least a year may be needed to see an effect on tau PET.

• Animal studies achieved up to 70% tau knockdown without observed adverse effects; CEO cited tolerated human tau loss-of-function variants and adult biological redundancy as support for potential safety.

Gene therapy safety and development

• Planned maximum dose is 5E13 vg/kg, below the 1E14 vg/kg range cited for systemic AAV therapies; the capsid showed 30-fold liver detargeting versus AAV9, with immunosuppression planned during administration.

• CEO said GLP toxicology included additional measurements informed by FDA discussions after a gene therapy patient death; he characterized the toxicology findings as promising for safety.

• Alzheimer’s trials would likely be larger than rare-disease studies and powered for CDR-SB; CEO envisioned a once-and-done IV treatment as a possible baseline therapy, with commercial success at a lower price supported by volume.