Cognition Therapeutics Inc.?s mission is to develop effective therapeutics for Alzheimer?s disease (AD). Recent scientific discoveries have identified oligomers of the brain protein Amyloid beta 42 (A?Os) as toxic culprits in disease progression. Cognition has identified a subset of sigma-2 receptor binding modulators that displace A?Os from neurons and block the downstream pathological signaling that inhibits memory formation. This approach is in contrast to traditional A?O intervention strategies, which either block the expression of Abeta or clear A?Os or block their formation. These compounds should prevent further A?O-induced damage, and unmask existing memory capacity as synapses recover. These receptor binding modulators are hypothesized to be disease-modifying treatments that would be effective throughout the course of the disease, and significantly impact the lives of the millions of Alzheimer?s patients. Pharmaceutical industry efforts targeted specifically at A?O displacement are currently limited. Cognition Therapeutics is one of the only companies uniquely focused on discovery of small molecule A?O-displacing therapeutics. Cognition Therapeutics has discovered two CNS drug-like series of A?O-displacing compounds, Analogs of both series displace oligomers from neurons and completely block A?O-induced membrane trafficking changes and synapse loss. Members of these series are highly brain-penetrant and completely block oligomer-induced memory deficits in Alzheimer?s disease mouse models. Drug candidate CT1812 from Series 1 is progressing through clinical trials. Cognition now seeks to leverage the accumulated knowledge of SAR from both series plus the known sigma-2 receptor binding modulators to define and develop new lead candidates for the clinical pipeline. Additional candidates with different physicochemical and structural properties would de-risk the clinical development-to-NDA process for these first-in-class treatments. This proposal will allow us to expand our portfolio of A?O-displacing molecules with the goal of identifying orally efficacious candidates for further development as therapeutics for AD.

Public Health Relevance

Cognition Therapeutics Inc.?s mission is to develop effective therapeutics for Alzheimer?s disease which target the toxic Abeta oligomer (A?O) protein. In contrast to other A?O intervention strategies, which either block the expression of Abeta or clear A?Os or block their formation, Cognition Therapeutics (CogRx) has chosen a novel ?oligomer displacement? approach to targeting A?Os, using compounds to displace oligomers from their binding site on neuronal synapses. This approach protects neurons from toxic oligomer assault and allows them to regenerate lost synapses. We have discovered and developed two orally available CNS drug-like lead series of sigma-2 receptor modulators that displace the A?O protein from neuronal cells in the brain. Analogs from both series prevent memory deficits in Alzheimer?s disease mouse models. This proposal requests funding in order to discover and develop new leads for the clinical pipeline, leveraging our accumulated knowledge of the structure-activity relationships of both series as well as known sigma-2 receptor modulators. Successful advancement of a A?O-displacing drug would significantly impact the lives of the 35 million patients worldwide suffering from AD and MCI, for whom no disease-modifying treatment exists.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AG055206-03
Application #
9710579
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Martin, Zane
Project Start
2017-09-15
Project End
2020-04-30
Budget Start
2019-05-15
Budget End
2020-04-30
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Cognition Therapeutics, Inc.
Department
Type
DUNS #
808434612
City
Pittsburgh
State
PA
Country
United States
Zip Code
15203