Tau lags amyloid, but Bristol Myers sees potential

Targeting tau as a mechanism to treat Alzheimer’s disease is very much second fiddle to the amyloid-targeting therapies that are on, or fast approaching, the market. But the Bristol Myers Squibb’s move this month to license Prothena’s anti-tau MAb PRX005 shows that the strategy is not dead. Bristol Myers has paid $55m for rights to the asset, which is in phase 1 trials. PRX005 binds to the microtubule binding region of tau – the same part Eisai’s E2814 targets, so data from the two phase 3 trials E2814 is currently in could give an idea of PRX005’s chances. But E2814’s studies won’t read out until 2027. Meanwhile, phase 2 trials of three tau-targeting agents are set to read out this year or next. One of the most closely watched is Lilly’s O-GlcNAcase enzyme inhibitor LY3372689. Blocking this enzyme is thought to prevent formation of tau, and the ongoing trial, which includes two doses and a placebo arm, will assess the agent’s ability to slow cognitive decline on the integrated Alzheimer's disease rating scale.