Voyager Reports Positive Topline Data for Single Ascending Dose (SAD) Trial of Anti-Tau Antibody VY7523 and Initiates Multiple Ascending Dose (MAD) Trial in Alzheimer’s Disease

Rhea-AI Summary

Voyager Therapeutics (VYGR) has announced positive topline data from its single ascending dose (SAD) trial of VY7523, an anti-tau antibody designed to inhibit pathological tau spread in Alzheimer's disease. The trial, involving 48 healthy volunteers across six dose cohorts, demonstrated safety, tolerability, and dose-proportional pharmacokinetics.

Key findings include:

• No serious adverse events or infusion reactions reported
• Dose-proportionate increase in serum concentrations
• Cerebrospinal fluid-to-serum ratio of 0.3%, aligning with other approved AD antibodies

The company has initiated a multiple ascending dose (MAD) trial involving 52 patients with early Alzheimer's disease. This study will evaluate safety, tolerability, and VY7523's ability to prevent pathologic tau spread through PET imaging. Initial tau PET imaging data is expected in H2 2026.

Positive

• Successful completion of SAD trial with positive safety profile
• No serious adverse events or infusion reactions reported
• Dose-proportional pharmacokinetics achieved
• CSF-to-serum ratio matches approved AD antibodies
• Preclinical data showed 70% reduction in tau spread

Negative

• Initial tau PET imaging data not available until H2 2026
• Early-stage trial results - efficacy yet to be proven

Insights

Biotechnology Research Analyst

Voyager Therapeutics has achieved a significant clinical milestone with positive topline data from their Single Ascending Dose (SAD) trial for VY7523, an anti-tau antibody targeting Alzheimer's disease. The data revealed that VY7523 demonstrated safety, tolerability, and dose-proportional pharmacokinetics across all six dose cohorts tested in healthy volunteers, with no serious adverse events reported.

What's particularly notable in the results is the cerebrospinal fluid-to-serum ratio of 0.3%, which aligns with other FDA-approved monoclonal antibodies for Alzheimer's disease. This bioavailability marker suggests the compound can reach its intended target in the central nervous system at levels comparable to existing treatments.

Based on these promising results, Voyager has initiated the Multiple Ascending Dose (MAD) trial involving 52 patients with early Alzheimer's disease. This phase will evaluate whether VY7523 can actually prevent the spread of pathological tau protein, with initial tau PET imaging data expected in H2 2026.

The advancement into patient trials represents a de-risking event for this clinical program, as safety and pharmacokinetic profiles have cleared the first regulatory hurdle. Voyager's dual-approach strategy targeting tau pathology (both with this antibody and a separate tau-silencing gene therapy) provides multiple shots on goal in addressing one of the fundamental pathological mechanisms of Alzheimer's disease.

Neuroscience Medical Specialist

The VY7523 antibody's mechanism of action addresses a compelling target in Alzheimer's pathology. Unlike earlier generations of Alzheimer's treatments that primarily focused on amyloid beta, this compound targets pathological tau protein, which correlates more closely with cognitive decline and disease progression.

The preclinical data showing a 70% reduction in tau spread is scientifically significant, as tau propagation from cell to cell is believed to drive disease progression. VY7523's specificity for a unique C-terminal epitope potentially differentiates it from other tau-targeting approaches in development.

The study design progression from healthy volunteers to patients with early Alzheimer's follows standard clinical development protocols, but the real test will come from the MAD trial's tau PET imaging endpoints. These biomarker measurements will provide the first evidence of whether the antibody can actually engage its target and modify the disease process in patients.

It's important to note that while receiving clearance to advance to patient trials is positive, the timeline to meaningful efficacy data extends to late 2026. This extended development horizon is typical for neurodegenerative disease programs, where changes in disease biomarkers and clinical symptoms take significant time to measure. The absence of infusion reactions in the SAD study is particularly encouraging for a monoclonal antibody therapy, as these reactions can limit dosing and patient compliance.

- Topline SAD data from healthy volunteers demonstrate safety, tolerability, and dose-proportional pharmacokinetics, supporting potentially best-in-class profile -

- MAD study initiated in patients with early Alzheimer’s disease; initial tau PET imaging data expected in H2 2026 -

LEXINGTON, Mass., March 03, 2025 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (Nasdaq: VYGR), a biotechnology company dedicated to advancing neurogenetic medicines, today announced positive topline data from the Company’s single ascending dose (SAD) trial of VY7523, an investigational anti-tau antibody developed to selectively inhibit the spread of pathological tau in Alzheimer’s disease (AD). In the SAD trial, data on VY7523 delivered intravenously demonstrated safety, tolerability, and dose-proportional pharmacokinetics (PK). Voyager has initiated a multiple ascending dose (MAD) trial of VY7523 in patients with early AD, which is expected to generate initial tau positron emission tomography (PET) imaging data in the second half of 2026.

“We continue to view tau as the most exciting target in Alzheimer’s disease, which is why we are advancing two tau-targeting approaches, our anti-tau antibody and our tau silencing gene therapy,” said Toby Ferguson, M.D., Ph.D., Chief Medical Officer of Voyager Therapeutics. “For the antibody approach, we believe VY7523 could be best-in-class due to the emerging PK data and previous preclinical data showing 70% reduction in tau spread, as well as its specificity for pathological tau and for a unique C-terminal epitope. We look forward to third-party data later this year and early next year, which could continue to build excitement around tau ahead of our VY7523 tau PET data.”

The SAD study was a randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability, and pharmacokinetics of single intravenous (IV) doses of VY7523 in 48 healthy volunteers. VY7523 was well tolerated across all six ascending dose cohorts, meeting the primary objective of the trial, with no serious adverse events (SAEs), severe adverse events, or infusion reactions reported. Secondary objectives of the trial were also met. Serum concentrations increased in a dose-proportionate manner, and the cerebrospinal fluid (CSF)-to-serum ratio was 0.3%, consistent with other monoclonal antibodies approved for the treatment of AD. Voyager expects to present additional data from the SAD study at an upcoming scientific conference.

The MAD study is a randomized, double-blind, placebo-controlled trial to evaluate VY7523 in 52 patients with early AD (mild cognitive impairment due to AD or mild AD). The primary endpoint is safety and tolerability. Key secondary endpoints include the ability of VY7523 to prevent the spread of pathologic tau, as measured by tau PET imaging. Initial tau PET imaging data are expected in the second half of 2026. Additional secondary endpoints include immunogenicity and pharmacokinetic parameters.

About VY7523
VY7523 is an IV-administered, recombinant, humanized IgG4 monoclonal antibody developed to inhibit the spread of pathological tau, which is closely correlated with disease progression and cognitive decline in Alzheimer’s disease. VY7523 is selective for pathological tau and targets a specific C-terminal epitope of tau. In preclinical in vivo studies, the murine version of VY7523 inhibited seeding and spread of pathological tau by approximately 70%. In a single ascending dose study in healthy volunteers, data on VY7523 demonstrated safety, tolerability, and dose-proportional pharmacokinetics. Voyager is currently assessing VY7523 in a multiple ascending dose trial in patients with early Alzheimer’s disease and expects initial tau PET imaging data in the second half of 2026.

About Alzheimer’s Disease
Alzheimer’s disease is a progressive neurodegenerative disease estimated to affect 7 million people in the U.S.^I and up to 416 million people globallyⁱⁱ. The disease causes memory loss and may escalate to decreased independence, communication challenges, behavioral disorders such as paranoia and anxiety, and lack of physical controlⁱⁱⁱ. In 2023, the total cost of caring for people living with Alzheimer’s and other dementias in the U.S. was estimated at $345 billion^iv.

About Voyager Therapeutics
Voyager Therapeutics, Inc. (Nasdaq: VYGR) is a biotechnology company dedicated to leveraging the power of human genetics to modify the course of – and ultimately cure – neurological diseases. Our pipeline includes programs for Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and multiple other diseases of the central nervous system. Many of our programs are derived from our TRACER™ AAV capsid discovery platform, which we have used to generate novel capsids and identify associated receptors to potentially enable high brain penetration with genetic medicines following intravenous dosing. Some of our programs are wholly owned, and some are advancing with partners including Alexion, AstraZeneca Rare Disease; Novartis Pharma AG; and Neurocrine Biosciences, Inc. For more information, visit www.voyagertherapeutics.com.

Voyager Therapeutics^® is a registered trademark, and TRACER™ is a trademark, of Voyager Therapeutics, Inc.

Forward-Looking Statements

This press release contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as “expect,” “potential,” “believe,” “could,” or “continue,” and other similar expressions are intended to identify forward-looking statements.

For example, all statements Voyager makes regarding Voyager’s ability to advance its tau antibody program, including expectations for Voyager’s achievement of clinical development milestones for VY7523, such as clinical trial enrollment and the generation of clinical data; the commercial potential for VY7523; Voyager’s expectations for the presentation of additional data from the SAD trial at a future scientific conference; and the potential for third-party clinical data to inform third-party interest in tau-targeting product candidates or Voyager’s clinical development plans are forward looking.

All forward-looking statements are based on estimates and assumptions by Voyager’s management that, although Voyager believes such forward-looking statements to be reasonable, are inherently uncertain and subject to risks and uncertainties that may cause actual results to differ materially from those that Voyager expected. Such risks and uncertainties include, among others, the expectations and decisions of regulatory authorities; the timing, initiation, conduct and outcomes of Voyager’s preclinical and clinical studies; the availability of data from clinical trials; the availability or commercial potential of product candidates under collaborations; the success of Voyager’s product candidates; the willingness and ability of Voyager's collaboration partners to meet obligations under collaboration agreements with Voyager; the continued development of Voyager’s technology platforms, including Voyager’s TRACER platform and its antibody screening technology; Voyager’s scientific approach and program development progress, and the restricted supply of critical research components; the development by third parties of capsid identification platforms that may be competitive to Voyager’s TRACER capsid discovery platform; Voyager’s ability to create and protect intellectual property rights associated with the TRACER capsid discovery platform, the capsids identified by the platform, and development candidates for Voyager’s pipeline programs; the possibility or the timing of Voyager’s receipt of program reimbursement, development or commercialization milestones, option exercise, and other payments under Voyager’s existing licensing or collaboration agreements; the ability of Voyager to negotiate and complete licensing or collaboration agreements with other parties on terms acceptable to Voyager and the third parties; the success of programs controlled by third-party collaboration partners in which Voyager retains a financial interest; the ability to attract and retain talented directors, employees, and contractors; and the sufficiency of Voyager’s cash resources to fund its operations and pursue its corporate objectives.

These statements are also subject to a number of material risks and uncertainties that are described in Voyager’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission. All information in the press release is as of the date of this press release, and any forward-looking statement speaks only as of the date on which it was made. Voyager undertakes no obligation to publicly update or revise this information or any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

Contacts
Trista Morrison, NACD.DC, tmorrison@vygr.com
Media: Brooke Shenkin, brooke@scientpr.com

References:

^{i. Alzheimer’s Association. 2024 Alzheimer’s Facts and Figures. Available at: https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf. Accessed January 9, 2025.
ii. Gustavsson A, Norton N, Fast T, et al. Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimer’s Dement. 2023; 19: 658–670. doi: 10.1002/alz.12694.
iii. Penn Medicine. The 7 Stages of Alzheimer’s Disease. Available at: https://www.pennmedicine.org/updates/blogs/neuroscience-blog/2019/november/stages-of-alzheimers. Accessed January 9, 2025.
iv. USAgainstAlzheimer’s. The Alzheimer’s Disease Crisis – By the Numbers. Available at: The Alzheimer’s Disease Crisis – By the Numbers | UsAgainstAlzheimer’s (usagainstalzheimers.org). Accessed: January 9, 2025.}

FAQ

What were the key results of VYGR's VY7523 single ascending dose trial?

The trial demonstrated safety, tolerability, and dose-proportional pharmacokinetics across all six dose cohorts, with no serious adverse events or infusion reactions reported.

How many patients will be enrolled in VYGR's VY7523 multiple ascending dose trial?

The MAD trial will enroll 52 patients with early Alzheimer's disease (mild cognitive impairment due to AD or mild AD).

When will VYGR release initial tau PET imaging data for VY7523?

Initial tau PET imaging data from the MAD trial is expected in the second half of 2026.

What is the cerebrospinal fluid-to-serum ratio for VYGR's VY7523?

The CSF-to-serum ratio was 0.3%, consistent with other monoclonal antibodies approved for Alzheimer's disease treatment.

What are the primary and secondary endpoints of VYGR's VY7523 MAD trial?

The primary endpoint is safety and tolerability, while key secondary endpoints include preventing pathologic tau spread (measured by PET imaging), immunogenicity, and pharmacokinetic parameters.