Discovery

NIH backs Jillion’s oral small-molecule tau program with USD 1.12m award

NIH backs Jillion’s oral small-molecule tau program with USD 1.12m award

Brooklyn, New York-based Jillion Therapeutics Inc. received a USD 1.12 million Phase II Small Business Innovation Research (SBIR) award from the National Institute on Aging (NIA) to advance orally available, brain-penetrant small-molecule inhibitors that directly bind pathological tau for Alzheimer's disease and other tauopathies.

The award went to a project led by principal investigator Marc Flajolet, supports preclinical optimization of compounds identified through Jillion's proprietary DNA-encoded library (DEL) platform. No oral disease-modifying therapy directly targeting tau pathology is currently approved for Alzheimer's disease.

In earlier Phase I SBIR work, Jillion used its DEL platform to identify small molecules that physically bind monomeric and oligomeric forms of tau, which aggregates and forms neurofibrillary tangles in Alzheimer's disease and other tauopathies. The Phase II program will validate prioritized hits in biochemical and cell-based assays, optimize potency and central nervous system exposure through medicinal chemistry, and evaluate brain penetration, safety, and efficacy in tauopathy mouse models.

The project aims to nominate one lead candidate and two backups for subsequent Investigational New Drug-enabling development. Jillion also intends to use the program to establish a broader approach for discovering small-molecule drugs against intrinsically disordered proteins such as tau.

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Other oral tau-directed approaches have reached clinical development. TauRx Therapeutics' hydromethylthionine mesylate, a tau aggregation inhibitor, has completed Phase III development in Alzheimer's disease and is under regulatory review in the UK. AC Immune and Eli Lilly are developing next-generation Tau Morphomer small-molecule aggregation inhibitors following completion of a Phase I study of earlier candidate ACI-3024. Merck and Alectos Therapeutics previously advanced the O-GlcNAcase inhibitor MK-8719 through Phase I, an indirect approach intended to reduce pathological tau formation by increasing O-GlcNAcylation.


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