FDA Grants Fast Track Designation to Anti-Tau Antibody BMS-986446 for Alzheimer Disease

The US Food and Drug Administration (FDA) has granted Fast Track designation to BMS-986446, an investigational anti-microtubule binding region (MTBR) tau antibody in phase 2 development for early Alzheimer disease (AD), Bristol Myers Squibb announced. Fast Track status is intended to facilitate drug development and expedite regulatory review for serious conditions with unmet medical needs.¹

AD, the most common form of dementia, is a progressive neurodegenerative disorder characterized by neuronal death and the accumulation of amyloid-beta and pathological tau proteins. Tau protein fragments containing MTBR have been implicated in the spread of neurofibrillary tangles and cognitive decline. BMS-986446 is designed to neutralize the spread of pathological tau and promote clearance, with the goal of slowing or delaying disease progression.^1,2

Preclinical data demonstrated that BMS-986446 reduced tau uptake and spread, protected against behavioral deficits, and localized with tau pathology in AD brain tissue. A phase 1 study in healthy participants showed the agent was safe and well tolerated across 3 dose cohorts, according to Bristol Myers.¹

BMS-986446 is currently being evaluated in the TargetTau-1 phase 2 trial (NCT06268886), a randomized, double-blind, placebo-controlled study in patients with early AD. The trial is fully enrolled and includes assessments of tau and amyloid-beta biomarkers alongside clinical outcomes to determine the effect of treatment on disease progression.¹

Mechanistically, BMS-986446 is a humanized monoclonal antibody that binds to multiple domains within the MTBR of tau (R1–R3) to prevent intercellular spread. In addition, the antibody activates microglia through its Fc receptor, facilitating tau clearance via phagocytosis.¹

Bristol Myers Squibb noted that the company is pursuing a continuum of care strategy in AD, including investigational therapies that target tau as well as symptomatic approaches for behavioral complications such as psychosis and agitation.¹

“The FDA’s Fast Track Designation for BMS-986446 underscores the urgent need for innovative therapies for Alzheimer’s disease and recognizes the potential of this investigational anti-MTBR-tau antibody to meaningfully alter the trajectory of disease progression,” Laura Gault, senior vice president, head of development, Neuroscience, Bristol Myers Squibb, said in a press release.¹ “Bristol Myers Squibb is taking a continuum of care approach to Alzheimer’s disease, studying investigational medicines such as those targeting tau to change the course of the disease as well as several symptomatic treatment options that can address severe shifts in behavioral symptoms, such as psychosis and agitation, that significantly impact patients and their caregivers.”

References:

1. Bristol Myers Squibb’s Anti-MTBR-Tau-Targeting Antibody, BMS-986446, Granted Fast Track Designation by U.S. FDA for the Treatment of Alzheimer’s Disease. Bristol Myers Squibb. News release. October 01, 2025. Accessed October 01, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibbs-Anti-MTBR-Tau-Targeting-Antibody-BMS-986446-Granted-Fast-Track-Designation-by-U-S--FDA-for-the-Treatment-of-Alzheimers-Disease/default.aspx
2. Alzheimer's Association. What is Alzheimer's Disease?. https://www.alz.org/alzheimers-dementia/what-is-alzheimers. Accessed October 1, 2025.