BMS-986446 Granted Fast Track Designation for the Treatment of Alzheimer Disease

Bristol Myers Squibb today announced that the US Food and Drug Administration (FDA) has granted Fast Track Designation to BMS-986446, a potential best-in-class anti-microtubule binding region-tau (anti-MTBR-tau) antibody in phase 2 development for the treatment of early Alzheimer disease (AD).¹

BMS-986446 is a humanized monoclonal antibody that targets multiple domains of the microtubule binding region of tau. This highly pathogenic tau fragment is associated with neurofibrillary tangle formation and cognitive decline in AD. BMS-986446 binds to specific regions of the tau protein to prevent the cell-to-cell spread of tau and tau uptake into cells. It also activates microglia through its Fc receptor function, promoting the clearance of tau via phagocytosis. By neutralizing the spread and promoting the clearance of pathological tau, BMS-986446 aims to modify the underlying course of the disease with the ultimate goal of slowing or delaying disease progression.

“The FDA’s Fast Track Designation for BMS-986446 underscores the urgent need for innovative therapies for Alzheimer disease and recognizes the potential of this investigational anti-MTBR-tau antibody to meaningfully alter the trajectory of disease progression,” said Laura Gault, the senior vice president and head of development, Neuroscience, at Bristol Myers Squibb. “Bristol Myers Squibb is taking a continuum of care approach to Alzheimer 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.”

In preclinical models, investigators noted that BMS-986446 demonstrated significant reductions in tau uptake and spread, protection against behavioral deficits, and was localized with tau pathology in AD brain tissue. BMS-986446 was also shown to be safe and well tolerated across 3 dose cohorts in a phase 1 study of healthy participants.²

TargetTau-1 is a randomized, double-blind, placebo-controlled, global phase 2 trial to evaluate the efficacy, safety, and tolerability of multiple doses of BMS-986446 in adults aged 50 to 80 years with early AD. The primary objective of the study is to evaluate clinical decline in participants treated with BMS-986446 compared with placebo. Investigators will evaluate whether targeting MTBR-tau can modify disease progression. The primary end point will be clinical decline evaluated based on mean change from baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score at 76 weeks. Secondary objectives include (1) assessing the effects of BMS-986446 on brain tau deposition, measured using PET, (2) determining whether treatment with BMS-986446 delays cognitive and functional decline, assessed using a selection of rating scales, and (3) evaluating safety. Exploratory endpoints include measures of BMS-986446 pharmacokinetics and immunogenicity, plasma biomarkers of AD, brain MRI changes, and quality of life assessments. This ongoing phase 2 study is fully enrolled. The estimated study completion date is November 2027.³

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. News release. October 1, 2025. Accessed October 1, 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. Martényi F, Campbell B, Kinney GG, et al. PRX005, a novel anti-MTBR tau monoclonal antibody: results from a first-in-human double-blind, placebo-controlled, single ascending dose phase 1 study. Alzheimers Dement. 2023;19(Suppl 21):e074181.

3. van Dyck C. TargetTau-1: A Phase II Trial Evaluating the Efficacy, Safety, and Tolerability of a Monoclonal Antibody Targeting the Tau Protein Microtubule Binding Region in Patients with Early Alzheimer’s Disease. Presentation at: 17th Clinical Trials in Alzheimer’s Disease Congress; October 29-November 1, 2024; Madrid, Spain. Accessed October 1, 2025. https://www.emjreviews.com/en-us/amj/neurology/symposium/targettau-1-a-phase-ii-trial-evaluating-the-efficacy-safety-and-tolerability-of-a-monoclonal-antibody-targeting-the-tau-protein-microtubule-binding-region-in-patients-with-early-alzheimers-s110325/