Inhibitors of Tau Oligomer Formation

Oligomerix is highly differentiated from its competitors in its approach targeting the self-association of individual tau proteins into small oligomeric aggregates allowing tau to revert back to its functional form. The Company has developed a lead series of compounds that have drug-like properties, can readily enter the brain, and can be used to target all types of tau aggregates. This small molecule approach enables treatment at all stages of disease and is a low cost therapeutic intervention or preventative relative to other forms of treatment such as antibody based therapeutics.

Target: Tau protein oligomers that inhibit neuronal signaling, impair memory formation, and cause neurotoxicity.

Approach: Develop small molecules reducing levels of tau oligomers to treat symptoms and inhibit/arrest disease progression.

Differentiation: Compound screening is performed with full length tau without mutations using conditions promoting oligomer formation, without the use of aggregation enhancers such as heparin that facilitate fibril formation, and without intercalating dyes. This approach best recapitulates tau oligomer formation associated with Alzheimer’s and related neurodegenerative diseases.

Outcome: Small molecules selected in vitro for inhibition of tau oligomer accumulation have demonstrated reduction of tau aggregation in several in vivo prevention and therapeutic mouse models.

Significance: Validation of platform to select and optimize small molecules for drug development.