Following the observation that tauC3 is responsible for a significant portion of tau seeding activity in AD, the murine mAb from which TBL-100 was developed (TBL-100m) was tested for its ability to block this activity in a FRET seeding assay. As indicated in Figure 5 below,TBL-100m was indeed found to exert a potent effect in blocking seeding, achieving more than 90% reduction in uptake/aggregation compared to control treatment (Nicholls et al., 2017).
Figure 5. Anti-TauC3 antibody is efficient at blocking tau seeding activity in HEK293 cells.
Notably, the FRET analysis showed that neuronal antibody internalization is not required for a beneficial effect. It is possible, however, that internalized TBL-100 could produce added benefit by also preventing the neurotoxicity associated with intracellular tauC3.
TAU BIO-LOGIC is now developing TBL-100 for the treatment of AD and PSP. The humanized antibody has an affinity for tauC3 of 13pM (about 100-fold higher than most marketed therapeutic antibodies have for their target) and a specificity that is 1000-fold greater than for full length tau. The high affinity and specificity of the antibody are expected to translate into improved efficacy and safety compared to other tau antibodies currently in development.