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Cortexyme Inc. presents data from its Phase 1b trial of the gingipain inhibitor COR388, showing reduced ApoE fragmentation in treated participants

Saturday 07 December 2019

On 7 December, Cortexyme Inc. presented data from a Phase 1b trial of its investigational product COR388, showing that participants treated with COR388 had reduced levels of fragmented ApoE proteins in samples of their cerebrospinal fluid (CSF). COR388 is a small-molecule inhibitor of gingipains, which are proteins that are released by bacteria species (p.gingivalis) that commonly reside in the mouth.  Previous studies have shown that people with bacterial gum disease have a higher risk of developing Alzheimer’s disease (AD), and that people with AD have elevated levels of gingipain in their brains, associated with infiltratingp.gingivalisbacteria.  Cortexyme believe that gingipains cleave proteins such as ApoE and Tau, inducing neurotoxicity – and that inhibiting gingipains may therefore confer therapeutic benefits. 

The Phase 1b trial of COR388 was designed to test the safety and initial clinical efficacy of the drug in a small number of participants with AD compared to healthy controls.   In this trial, six participants with AD received a 50mg dose of COR388 twice daily for 28 days, while 3 participants received a placebo.  After this dosing period, the participants who received COR388 showed substantial reductions in ApoE fragments in their CSF. Alongside,in vitroexperiments showed that cells infected withp.gingivalisbacteria had much higher levels of ApoE cleavage activity. Treatment of infected cells with COR388 blocked ApoE fragmentation, suggesting that it can effectively inhibit gingipain activityin vitro. A large, international Phase 2/3 Trial of COR388 (the GAIN Trial) is currently underway. The GAIN Trial is evaluating the efficacy, safety, and tolerability of COR388 in participants with mild to moderate AD. Top-line results are expected in late 2021.  Link to press release: