BBS MAb is an immunotherapeutic product for AD. It has been shown by several groups that antibodies, either administered by injection or elicited by a vaccine, have immunotherapeutic activity in preventing disease progression in animal models of AD. However, clinical studies with both approaches, including Phase 3 studies, have given disappointing results. The BBS MAb has a novel mechanism of action that makes it distinctive and that could offer certain safety and efficacy advantages over other immunotherapeutic and small-molecule approaches for AD. The primary BBS product candidate is a MAb; there also is an active vaccine that would elicit antibodies of similar specificity as the MAb. BBS is based on antibodies that interfere with the process that leads to the creation of amyloid-β (Aβ) intracellular oligomers and plaques and phosphorylated tau (p-tau) in the brains of symptomatic AD subjects. The cell-surface amyloid precursor protein (APP) is processed by enzymes, beginning with β-secretase (BACE), into Aβ peptides. The MAb binds to the BACE cleavage site on cell-surface APP without binding to Aβ, and thus is called BBS (Blocking β-site). The binding of BBS MAb to APP inhibits its processing into Aβ and other peptides through the endocytic pathway following rapid internalization to the cell, which reduces the occurrence of Aβ plaques and intracellular oligomers as well as p-tau neurofibrillary tangles within nerve cells, thus functioning early in the Aβ pathway compared with other immunotherapies that bind directly to Aβ plaques and so target only the late stage of AD pathogenesis. In vivo studies with BBS MAb in animal models of AD have demonstrated reductions in Aβ and p-tau levels, improved non-spacial and visual memory, and reductions in both brain inflammation and brain micro-hemorrhage. A second-generation MAb was developed with significantly higher affinity than the first-generation MAb; this new MAb is also effective in animal AD models, and its humanization is underway. Notably, the BBS MAb also is effective in a mouse model of amniolateral sclerosis (ALS). In addition, this approach is supported by a de-facto clinical proof-of-principle recently discovered in subjects with a point mutation in APP adjacent to the BACE cleavage site, which results in a 40% reduction in the cleavage of APP by BACE (similar to the percent reduction mediated by BBS MAb) and that is associated with a significantly reduced incidence of AD and improved cognition relative to subjects with native APP (http://www.ncbi.nlm.nih.gov/pubmed/22801501) – these data suggest that BBS MAb immunotherapy could bring a therapeutic benefit to AD subjects. The BBS MAb is being humanized for clinical trials.