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. 

Knowing where their tau is: mid- and late-stage tau-targeting projects 
Project Company Mechanism Status
Hydromethylthionine mesylate Taurx Pharmaceuticals Oral tau aggregation inhibitor Ph3 Lucidity trial failed Oct 2022; filed in UK, US filing planned
E2814 Eisai Anti-tau MAb (targets microtubule binding region) Ph2/3 Dian-Tu trial in early-onset Alzheimer's could report 2027; also in Ph3 Dian-Tu-001 basket trial which could report 2027
Remynd Calcium channel regulator; Tau aggregation inhibitor Ph2 trial in mild/moderate Alz could report imminently
LY3372689  Lilly O-GlcNAcase inhibitor Ph2 early Alz trial could report 2024
UCB/Roche Anti-tau MAb (targets central region) Ph2 trial in MCI/mild Alz could report topline data Q4 2024
INJ-63733657 Johnson & Johnson Anti-phospho-tau mAb Ph2 Autonomy trial in early Alz could report 2025
Biogen/Ionis Tau antisense oligonucleotide RNAi therapeutic Ph2 Celia trial in MCI or mild Alz dementia could report 2027
Roche/AC Immune Anti-tau MAb (targets N-terminus) Ph2 Lauriet trial in mild/moderate Alz met one of two co-primary endpoints in Nov 2021; open-label extension could report H2 2023
VAC 20121
AC Immune/J&J Anti-tau vaccine Interim data from ph1/2 trial in early Alz in Nov 2022 led to this project being chosen over JACI-35.054
Source: Evaluate Pharma, clinicaltrials.gov, company websites.

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