Synonyms: NI-105, 6C5 huIgG1/l
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: Biogen, Neurimmune
BIIB076 is a human recombinant, monoclonal anti-tau antibody generated by Neurimmune's reverse translational medicine platform. Biogen acquired it in 2010.
No cell-based or mouse preclinical work with this antibody has been published. At the 2017 AD/PD and AAIC conferences, Biogen reported that BIIB076 binds with subnanomolar affinity to human and cynomolgus monkey recombinant tau. It recognizes monomeric and fibrillar forms, as well as tau isolated from healthy human and Alzheimer's disease brains.
In young monkeys, a single 100 mg/kg dose of BIIB076 had a half-life in blood of eight to 11 days. It reached maximum CSF concentration in 24-48 hours but its CSF concentration was 1,000 times lower than in plasma. Using ultrasensitive single-molecule array (Simoa) assays to measure tau concentration in blood and CSF, Biogen reported that after BIIB076 administration, plasma total tau rose; CSF total tau stayed unchanged but free tau unbound to BIIB076 dropped 75 percent after 24 hours, returning to baseline after three weeks. This was taken to indicate CNS target engagement (April 2017 conference news).
A separate toxicity study evaluated three doses of up to 16 times the highest predicted efficacious dose, given intravenously or subcutaneously over the course of a month to 48 young cynomolgus monkeys, and compared to vehicle. Blood and CSF were sampled to measure BIIB076 and tau levels. This study reported no toxicology or pathology findings related to BIIB076, but did report dose-dependent increases in serum BIIB076 levels as well as exposure with subcutaneous delivery. CSF total and free tau was reported to be reduced at the highest doses used (Czerkowizc et al., 2017).
In February 2017, Biogen started a six-center Phase 1 trial in the U.S. aiming to enroll 56 healthy volunteers and people whose mild or probable AD was ascertained by CSF Aβ42, t-tau, and p-tau levels. This is an ascending-dose study giving a single intravenous infusion; healthy volunteers will be grouped into five successive dosing cohorts, AD patients into two. Primary outcomes were adverse events, clinical labs, vital signs, neurological exam, EKG, and MRI; secondary outcomes include eight pharmacokinetic parameters of exposure and clearance, as well as BIIB076 immunogenicity, all in blood. In June 2019, the company modified the trial protocol, reducing participant number to 48, dropping the more advanced AD cohort, and adopting adverse events as the sole primary outcome. The trial is set to run until February, 2020.
For all trials of BIIB076, see clinicaltrials.gov.
Last Updated: 31 Oct 2019
- Czerkowicz J, Chen W, Wang Q, Shen C, Wager C, Stone I, Stebbins C, Lamb M, Setser J, Cantone G, Graham D. Pan-Tau Antibody Biib076 Exhibits Promising Safety and Biomarker Profile in Cynomolgus Monkey Toxicity Study. Alzheimer's & Dementia, July 2017, Volume 13, Issue 7, Supplement, Page P1271
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