# Mechanism of action of oligomer-displacing Alzheimer investigation drug, CT1812:Receptor interactions and signaling pathways

> **NIH NIH R44** · COGNITION THERAPEUTICS, INC. · 2020 · $729,226

## Abstract

Aβ oligomers are considered the most toxic structural form of Amyloid beta, causing synaptotoxic changes
underlying cognitive decline in Alzheimer’s disease. CogRx has developed the world’s first highly brain
penetrant drug that selectively displaces oligomers from synaptic receptor sites and clears oligomers from the
brain into the cerebrospinal fluid (CSF). This first-in-class drug, CT1812, allosterically modulates a key protein
regulator of oligomer receptors (the sigma-2/PGRMC1 protein complex), destabilizing the oligomer binding
site, increasing the off-rate of AβOs and allowing rapid clearance into the CSF, however the interactions
between the receptor components and their role in downstream signaling pathways are unknown. CT1812
restores synapse number and cognitive performance to normal in AD mouse models. CT1812 has been
demonstrated to be safe and well-tolerated in healthy volunteers dosed once daily for 14 days in a placebocontrolled
Phase 1a trial, and is currently being evaluated in a follow-on placebo-controlled safety trial in AD
patients. The study will provide critical information about the mechanism of action of this innovative
differentiated and first in class compound. Successful commercialization of this drug will require partnership
with a large pharmaceutical company to support Phase 2 and 3 clinical trials and marketing, and detailed
understanding of the molecular mechanism of action of CT1812 has been cited by potential development
partners as being a critical requirement for engaging in such a partnership. CogRx has no other support
available for elucidating the details of CT1812’s mechanism of action. This Fast-Tract SBIR proposal will
provide crucial details about this novel mechanism of action and will enable the application of the proprietary
portfolio of sigma-2 ligands at CogRx to other diseases. This information will increase the chance for partnering
opportunities necessary for the clinical development of CT1812 for AD patients and will expand the pipeline
portfolio of CogRX into new clinical areas involving autophagy pathways.

## Key facts

- **NIH application ID:** 10002168
- **Project number:** 5R44AG062129-03
- **Recipient organization:** COGNITION THERAPEUTICS, INC.
- **Principal Investigator:** NICHOLAS JOHN IZZO
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $729,226
- **Award type:** 5
- **Project period:** 2018-09-30 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002168

## Citation

> US National Institutes of Health, RePORTER application 10002168, Mechanism of action of oligomer-displacing Alzheimer investigation drug, CT1812:Receptor interactions and signaling pathways (5R44AG062129-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10002168. Licensed CC0.

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