Bristol Myers Squibb announced that the U.S. Food and Drug Administration has granted Fast Track Designation to BMS-986446, a potential best-in-class anti-microtubule binding region-tau (anti-MTBR-tau) antibody currently in Phase 2 development for the treatment of early Alzheimer's disease. The designation is intended to facilitate development and expedite review of investigational drugs that treat serious conditions and fill an unmet medical need.
Novel Mechanism Targets Pathological Tau
BMS-986446 is a humanized monoclonal antibody that targets multiple domains of the microtubule binding region of tau, a highly pathogenic tau fragment associated with neurofibrillary tangle formation and cognitive decline in Alzheimer's disease. The antibody binds to specific regions of the tau protein (R1–R3 within the microtubule-binding domain) to prevent the cell-to-cell spread of tau and tau uptake into cells.
The therapeutic approach also activates microglia—the brain's immune cells—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.
Promising Preclinical and Early Clinical Data
In preclinical models, BMS-986446 demonstrated significant reductions in tau uptake and spread, protection against behavioral deficits and was localized with tau pathology in Alzheimer's brain tissue. The investigational therapy was also shown to be safe and well tolerated across three dose cohorts in a Phase 1 study of healthy participants.
"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," said Laura Gault, senior vice president, head of development, Neuroscience, Bristol Myers Squibb.
Phase 2 Trial Evaluates Disease Modification
The ongoing TargetTau-1 Phase 2 trial (NCT06268886) is a randomized, double-blind, placebo-controlled, global proof-of-concept study designed to evaluate the efficacy, safety and tolerability of multiple doses of BMS-986446 in participants with early Alzheimer's disease. The study is fully enrolled and aims to determine whether targeting MTBR-tau can modify disease progression.
In addition to clinical outcome measures, the trial integrates a comprehensive biomarker strategy to assess tau and amyloid-beta biology. The study includes several biomarkers of tau and amyloid-beta biology, as well as clinical outcome measures, to evaluate the impact of BMS-986446 on disease progression.
Addressing Critical Unmet Need
Alzheimer's disease is a progressive, multifaceted and devastating neurodegenerative disease and the most common type of dementia in adults. Changes in the brain disrupt communication between neurons, impacting memory, cognition and behavior. Pathological tau protein fragments containing the microtubule binding region appear to have a key role in the underlying pathology of Alzheimer's disease.
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.
