Voyager Therapeutics (NASDAQ:VYGR) CEO Al Sandrock outlined several 2026 priorities in a discussion focused on the company’s tau-directed pipeline and its newer blood-brain barrier (BBB)-penetrant capsid platform. Sandrock described 2026 as “the year of tau,” while also pointing to upcoming clinical entries that could provide early human proof-of-concept for Voyager’s capsids and a separate “brain shuttle” effort built from the same discovery work.
Voyager’s 2026 focus: tau programs, capsids in the clinic, and shuttle data
Sandrock framed three “pillars” for the year. First, Voyager has two assets directed against tau, including an antibody and a gene therapy approach. For the antibody, Sandrock said the company expects to report tau PET imaging data by year-end from a multiple ascending dose (MAD) study. The second tau program is a gene therapy tau knockdown asset that he characterized as similar to BIIB080, which he noted has an “important readout” expected in a mid-year timeframe.
Third, Sandrock said Voyager plans to share additional data on a shuttle platform—an outgrowth of its capsid discovery platform—designed to move therapeutics across the BBB.
How Sandrock contrasted tau and amyloid in Alzheimer’s disease
In discussing why Voyager is emphasizing tau, Sandrock said human genetics do not strongly implicate tau as a driver in Alzheimer’s disease, despite the fact that tau mutations can cause neurodegeneration in other conditions such as frontotemporal dementia.
He cited observations from a large PSEN1 familial Alzheimer’s cohort in Colombia, describing outliers who did not develop dementia in their early forties despite carrying a highly penetrant mutation. Sandrock said those individuals had extensive amyloid accumulation but did not show typical tau progression and did not develop dementia until their seventies, which he said “strongly implicates” tau as the key driver of dementia rather than amyloid.
Sandrock also described the natural history sequence in which amyloid pathway abnormalities appear first, followed later by tau accumulation and spread. He noted that Alzheimer’s staging (Braak and Braak) is based on where pathological tau has spread, and he differentiated initial tau changes that can occur in normal aging from the abnormal spread beyond regions such as the entorhinal cortex, which he linked to progression of disability in Alzheimer’s disease.
Tau knockdown gene therapy: broad distribution and regulatory interactions
On Voyager’s siRNA-based gene therapy, Sandrock emphasized the need for broad cortical distribution because tau pathology spreads across cortical regions. He said Voyager has evaluated multiple regions—including the hippocampus, entorhinal cortex, temporal cortex, and frontal cortex—and has seen knockdown “roughly this similarly” across cortical regions in the “50%–75% range,” which he said is comparable to BIIB080.
On regulatory strategy and safety, Sandrock said Voyager has had multiple interactions with the FDA, including a pre-IND meeting about a year earlier and a more recent Type C meeting aimed at incorporating the agency’s latest thinking on designing studies “in the safest possible way.” He said the company was not having difficulty interacting with FDA and described the discussions as helpful.
He said the near-term objective is demonstrating tau lowering in the brain, relying primarily on tau PET imaging. Sandrock highlighted that BIIB080’s phase 1 results showed a reduction from baseline in pathological tau by blocking new tau synthesis, which he described as a striking finding.
Tau antibody approach: epitope choice and tau PET goals
Sandrock addressed the rationale for Voyager’s antibody strategy amid past setbacks in the field. He said N-terminal anti-tau antibodies from Biogen and Eli Lilly failed to show an effect on tau PET imaging, while UCB’s bepranemab (a mid-domain antibody) affected the spread of pathological tau and also showed an effect on ADAS-Cog as a pre-specified secondary endpoint. However, he noted bepranemab failed on CDR sum of boxes, which he characterized as the primary endpoint FDA would expect in pivotal trials.
Voyager’s selection process, Sandrock said, prioritized antibodies specific for pathological forms of tau—consistent with a prion-like spread hypothesis—and relied on an animal model in which Alzheimer’s brain material is injected into a tau-expressing mouse to measure spread and identify antibodies that reproducibly block it. He said that model predicted failure of N-terminal antibodies and suggested bepranemab would block spread “somewhat,” while Voyager’s candidate performed better in that system.
For the upcoming MAD readout later in 2026, Sandrock said Voyager hopes to see a greater effect on the spread of pathological tau by tau PET imaging than bepranemab, with the longer-term goal of translating that into clearer clinical benefit. He added that Voyager’s study is too small to evaluate clinical outcomes directly.
Capsids and brain shuttles: timing, ALPL, and partnering strategy
On human proof-of-concept for Voyager’s BBB-penetrant capsids, Sandrock said the company plans to file an IND for its tau knockdown program in Q2, with the goal of entering the clinic in the second half of the year. He also said Neurocrine plans to file an IND and begin clinical work in Friedreich’s ataxia this year using one of Voyager’s capsids. Sandrock said evidence of safe dosing and brain gene expression could begin emerging next year, initially via fluid-based biomarkers, with tau PET imaging requiring more time.
For the shuttle platform, Sandrock said Voyager used capsids to identify BBB receptors and has discovered “five-eight” receptors, including ALPL, which he described as surprising given it is a GPI-anchored protein. He said Voyager has developed ALPL ligands intended to function as shuttles similar to transferrin receptor (TFR)-based approaches, but with different characteristics such as longer exposure, differing distribution patterns, and no observed effect on reticulocyte counts in their evaluations to date. He said the company is conducting non-human primate studies and will be evaluating safety carefully.
On potential safety concerns, Sandrock noted that severe loss of function of ALPL (greater than 70%) in humans can lead to hypophosphatasia, affecting bone and teeth mineralization, and he said the goal would be to “thread the needle” to avoid that level of loss of function.
From a business development perspective, Sandrock said Voyager expects to continue partnering. He cited five programs with Neurocrine, three with Novartis, and one with AstraZeneca (which he said inherited Pfizer’s rare disease portfolio). He highlighted deal structures where partners advance programs to IND and phase 1, while Voyager retains potential U.S. opt-in rights (he cited 40% for Friedreich’s ataxia and 50% for GBA1) alongside possible milestones and royalties.
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.
