The Therapeutic Landscape of Tauopathies: Evaluating the Tau Pipeline

Abstract

AbstractBackgroundMany disease modifying therapeutics for neurodegenerative diseases (NDs) have focused on the reduction of amyloid, neuroinflammation and synaptic plasticity. Many NDs include tau pathology either with amyloid deposits or without. These NDs can collectively classified as tauopathies. We have provided an overview of the therapeutic landscape of programs targeting tauopathies covering drug candidates in the clinical development as well as programs still in discovery and the preclinical stages.MethodSearch results from targeted queries and key word searches for MAPT and tau were carried out on GlobalData and SciFinder databases as the principal sources of information. Company websites, PubMed and conference proceedings were also researched for additional information. All data presented here is current to Aug. 31, 2022. All therapeutics in clinical phases I, II and III, as well as in preclinical development and discovery phase were included.ResultThe majority of therapeutic approaches focused on tau by directly targeting Microtubule Associated Protein Tau (MAPT) although indirect mechanisms also afford strategies that may ultimately affect tau. Our search through the end of August 2022 showed that the tau landscape currently contains 160 compounds, of which 38 are in clinical development. Of those, a total of 135 drugs directly target MAPT, with 33 of them combining MAPT with other mechanisms, mostly alpha synuclein (α‐syn) or amyloid protein targets. There is a growing variety of modalities that are being explored in targeting tau, with small molecules remaining dominant accounting for approximately 44% of all molecules in development. There were 18 therapies in both phase I and phase II clinical trials, and only one currently in phase three. There were also two therapies currently with an IND/CTA filing in process.ConclusionThere has been a significant increase in the number of researchers focusing on tau as a main therapeutic approach. The landscape of anti‐tau therapeutic agents is growing but special consideration should be given to primary tauopathies which do not share the amyloid burden of other NDs like Alzheimer’s disease, and do not share in the recent success of approved anti‐amyloid therapeutics.