Voyager Therapeutics (NASDAQ:VYGR) outlined what CEO Al Sandrock described as three “pillars of value” for the year ahead during a discussion at Oppenheimer’s 36th Annual Life Science Conference, pointing to advancing two tau-directed programs, initiating two gene therapy clinical entries using its blood-brain barrier-penetrant capsids, and building out its emerging NeuroShuttle platform for brain delivery of therapeutics.
Sandrock also said the company is “well capitalized” with cash runway “into 2028.”
Three pillars: tau, gene therapy, and NeuroShuttle
- Tau-targeted therapeutics, with “two shots on the tau target.”
- Gene therapy, with plans to put two assets into the clinic this year using its novel capsids, including a partnered Neurocrine program and a wholly owned Voyager program.
- NeuroShuttle, a platform based on receptors capable of delivering capsids into the brain, adapted into “shuttles” intended to bring other drug modalities into the central nervous system.
Sandrock’s view of tau as an Alzheimer’s target
In response to questions about external validation of tau in Alzheimer’s disease, Sandrock argued that tau spread follows a “very stereotypic manner” and is central to disease staging. He said tau pathology is “better correlated with clinical decline than actually even amyloid,” citing examples in which patients can have substantial amyloid burden without dementia until tau begins to spread.
He also said 2025 is likely to bring additional clarity from third-party readouts across modalities, including upcoming data presentations from Johnson & Johnson at ADPD and work from Biogen in tau-directed approaches.
Anti-tau antibody program VY7523: early safety/PK and a tau PET focus
Voyager’s lead anti-tau antibody, VY7523, has completed enrollment in the multiple ascending dose (MAD) portion of its phase 1 study, according to Sandrock. He said data evaluated so far have focused on preliminary safety and pharmacokinetics from earlier work, describing the antibody as “very safe,” consistent with what has generally been seen for anti-tau antibodies as a class.
On pharmacokinetics, Sandrock said the cerebrospinal fluid (CSF)-to-serum ratio was about 0.3%, within the typical monoclonal antibody range of roughly 0.1% to 0.5%. He added that the half-life supports once-monthly (every four weeks) dosing used in the MAD study.
Looking ahead to the MAD readout expected in the second half of the year, Sandrock emphasized that the study was designed specifically to assess tau PET imaging, saying it is powered to detect an effect on slowing the spread of pathological tau.
He cautioned against overreliance on fluid biomarkers, noting that in a Biogen study of an antibody that failed to affect clinical measures or tau PET imaging, a commonly used fluid biomarker (MTBR tau) still fell by about 40%. For Voyager, he said fluid biomarkers will be assessed, but he characterized them more as potential target-engagement markers compared with tau PET imaging, which he called the “key endpoint.”
Sandrock said Voyager would likely need a partner to proceed beyond the current work, describing Alzheimer’s development as too large for a small company to pursue deep into later stages alone. He said he has “always said” a partner would be needed for phase 3 and suggested even phase 2 could be difficult for Voyager to fund independently.
Interpreting mixed tau antibody data and the importance of epitope
Sandrock discussed UCB’s bepranemab as the first antibody to show an effect on tau spread, along with a signal on ADAS-Cog as a secondary endpoint, but with a negative primary endpoint (CDR-SB). He called this a “mixed” result that nonetheless demonstrated biological impact on tau spread.
He also previewed how he plans to interpret forthcoming J&J data, focusing less on the already-announced lack of clinical benefit and more on whether the antibody affected the spread of pathological tau on imaging. If it did not, he said lack of clinical benefit would be unsurprising; if it did block spread strongly yet still did not show a clinical effect, he said that could raise broader questions about whether the antibody approach is the right strategy.
Sandrock repeatedly returned to the concept that epitope selection may be critical. He said Voyager had evaluated an antibody against a similar epitope to J&J’s and opted not to advance it because it did not block tau spread well in the company’s spreading model using human Alzheimer’s material. He compared this to amyloid, where he said N-terminal antibodies worked while mid-domain and C-terminal antibodies did not, and expressed hope that, for tau, C-terminal antibodies like Voyager’s could prove more effective.
VY-1706 tau silencing gene therapy: IV, low dose, and broad CNS distribution
Sandrock outlined Voyager’s second tau “shot on goal” as VY-1706, a gene therapy approach intended to reduce tau expression broadly in the brain. He contrasted gene-silencing approaches with antibodies, which he said only bind extracellular tau, while knockdown can reduce “all forms of tau throughout the brain.”
Discussing comparisons to Biogen’s intrathecal antisense program BIIB080, Sandrock said BIIB080 achieved roughly a 60% reduction and that Voyager is targeting a 50% to 70% range. He said Voyager observed 50% to 70% knockdown in non-human primates at what he described as a “pretty low dose” of 1.3 × 1013 vg/kg, about an order of magnitude below typical intravenous AAV doses.
He also highlighted capsid engineering intended to reduce liver exposure, saying Voyager’s capsid “de-targets the liver by 30-fold,” and noted the industry’s awareness of liver toxicity risks in systemically delivered gene therapies.
On regulatory timing, Sandrock said Voyager had a productive FDA interaction roughly a year prior covering GLP toxicology and early trial design considerations. He said Voyager expects to file an IND in the second quarter and dose the first patient in the second half of the year. While the company has not disclosed full trial design details, he indicated tau PET imaging will be a central focus.
Sandrock also distinguished BIIB080’s intrathecal route—which he said creates a gradient of exposure from the lumbar cistern upward, with lowest levels in deep gray structures—from Voyager’s one-time IV approach, which he said leverages vasculature for broad CNS distribution without the same gradient and produces siRNA continually in the brain.
NeuroShuttle: ALPL as an alternative to transferrin receptor shuttles
On Voyager’s NeuroShuttle platform, Sandrock discussed ALPL as a brain delivery target and contrasted it with transferrin receptor (TFR) shuttles. He said TFR shuttle drugs tend to have short half-lives and distribute broadly to other tissues such as heart and muscle, and he noted hematologic adverse events observed with TFR approaches, including decreased reticulocyte counts.
Sandrock said ALPL appears differentiated so far by having a longer half-life due to different body distribution and that Voyager has seen “no effect on reticulocyte count” to date, while emphasizing the platform is still early. He suggested a longer half-life could be advantageous for targets requiring continuous coverage.
In terms of modalities, Sandrock said Voyager is exploring shuttling of antibodies, peptides, and oligonucleotides. He argued that successful shuttling of oligonucleotides could reduce the need for frequent intrathecal dosing and help avoid distribution gradients, potentially enabling less frequent IV administration.
Neurocrine partnership: FA clinic entry expected this year
On partnered programs with Neurocrine, Sandrock said Neurocrine has stated that its FA program using a TRACER-derived capsid is expected to enter the clinic this year, with an IND filing planned this year and movement into the clinic also anticipated this year. He added that Neurocrine has said the GBA program is progressing, though Neurocrine has not provided timing for clinic entry, and he noted Neurocrine has indicated other partnered programs are also progressing.
About Voyager Therapeutics (NASDAQ:VYGR)
Voyager Therapeutics, Inc is a clinical-stage biotechnology company focused on the development of gene therapies for serious neurological diseases. The company’s core activities center on the design and delivery of engineered adeno-associated viral (AAV) vectors tailored to target cells in the brain and central nervous system. Through its proprietary CapsidMap and VectorMap platforms, Voyager aims to enhance vector potency, specificity and durability to address diseases with high unmet medical need.
The firm’s pipeline includes several AAV-based candidates in preclinical and early clinical development.
