Voyager Therapeutics has added a new programme that modulates the expression of apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer’s disease (AD). 

The programme uses a proprietary intravenous (IV)-delivered, blood-brain barrier (BBB)-penetrant TRACER capsid to deliver a bifunctional payload that is designed to decrease expression of APOE in carriers of the variant APOE4, while delivering the variant APOE2.  

APOE4 has been strongly linked with a higher risk of developing AD, with almost all APOE4 homozygotes exhibiting AD pathology, while APOE2 has been associated with a lower risk of developing AD. 

In preclinical studies, a single IV injection of a TRACER capsid carrying the single bifunctional vector resulted in significant reductions of endogenous APOE4 in key AD-relevant brain regions of APOE4 knock-in mice, while significantly increasing expression of the APOE2 isoform to maintain overall APOE levels.  

Voyager anticipates presenting early data on this programme at an upcoming scientific meeting in 2025. 

“The Voyager team is leveraging our deep expertise in Alzheimer’s disease biology and drug development to advance multiple programs against what we believe to be the three most-promising targets: tau, amyloid, and APOE,” said Alfred Sandrock Jr, Chief Executive Officer of Voyager. “We believe each of these approaches will have an important role to play in the treatment of Alzheimer’s disease, particularly as the field begins to understand how best to sequence and combine treatments to improve outcomes for patients.” 

Voyager’s AD assets:
  • VY7523, a pathologic-specific anti-tau antibody, which is being evaluated in a multiple ascending dose (MAD) clinical trial in AD patients, with initial tau positron emission tomography (PET) data expected in the second half of 2026. 
  • VY1706, an IV-delivered tau silencing gene therapy that has shown up to 73% knockdown of tau mRNA in non-human primates following a single IV dose and is advancing towards IND in 2026. 
  • A vectorised anti-Aβ antibody gene therapy, which demonstrated over 15-fold greater brain-to-plasma ratio after a single IV dose compared to a passively administered antibody over four weeks in a murine model. 
  • The APOE gene therapy programme, which is designed to knock down APOE in APOE4 carriers while delivering APOE2 and maintaining total APOE levels. 

Diana Turner, Senior Digital Content Editor, DDW