Pipeline &

Clinical Trials


Candidate Selection

IND Enabling

Phase I

Phase II

Phase III

Atuzaginstat (COR388) / Lysine gingipain inhibitor - Alzheimer’s disease


Atuzaginstat (COR388) / Lysine gingipain inhibitor - Parkinson's disease


COR588 / Lysine gingipain inhibitor - Periodontal disease and other P. gingivalis indications


COR852 / Arginine gingipain inhibitor


COR817 / 3CL pro inhibitor - Coronavirus


Additional pipeline programs


*Cortexyme owns worldwide rights to all programs

Cortexyme recently completed testing its lead small molecule atuzaginstat (COR388) in a Phase 2/3 clinical study for the treatment of Alzheimer’s disease and reported top-line results that demonstrated a relationship between reduction of P. gingivalis infection and slowing of cognitive decline. While not meeting statistical significance on its co-primary cognitive and functional endpoints in the overall cohort, prespecified cohorts representing up to half of the GAIN Trial participants based on P. gingivalis infection level showed trends to approximately 50% slowing of cognitive decline in the 12-month study. The GAIN Trial included a sub-study for proof of efficacy in periodontal disease, which demonstrated a trend to benefit on the primary clinical endpoint of pocket depth in the same pre-specified sub-group with P. gingivalis DNA detectable in saliva. Most adverse events were mild to moderate in severity. The most common were gastrointestinal, such as diarrhea in up to 16% and nausea in 6% of participants treated with atuzaginstat vs. 3% and 2% of placebo participants, respectively.  Atuzaginstat was associated with dose-related liver enzyme elevations >3X the upper limit of normal: 2% on placebo, 7% on 40 mg BID, and 15% on 80 mg BID. These elevations alone were not clinically significant, and virtually all participants were asymptomatic. Two participants in the 80 mg BID arm had concomitant bilirubin elevations without alternative explanation. Lab changes resolved while participants remained on drug or after withdrawal without any known long-term adverse effects. Atuzaginstat treated groups showed no increase in ARIA (amyloid-related imaging abnormalities), including microhemorrhage and edema, or superficial siderosis. Atuzaginstat is a novel virulence factor inhibitor targeting gingipains from P. gingivalis that have been found in the brain of Alzheimer’s patients. Infection of mice with P. gingivalis results in brain infiltration and downstream pathology of Alzheimer’s disease, including Abeta42 production, neuroinflammation, and neurodegeneration that can be blocked by atuzaginstat. Additional compounds from our proprietary protease inhibitor library are advancing through preclinical development and IND enabling studies.

Clinical Trials

Current Studies

In September 2021, Cortexyme expanded its proprietary development pipeline with the initiation of a Phase 1 clinical trial of COR588, a second-generation small-molecule lysine-gingipain inhibitor differentiated from the company’s lead drug candidate atuzaginstat (COR388) by its improved pharmacokinetic properties and anticipated once daily oral administration. Delivering on its commitment to bring innovation to high unmet clinical needs, Cortexyme expects COR588 to be targeted for use in the treatment of periodontal disease and other P. gingivalis-related indications.

The GAIN Clinical Trial

Completed in October 2021, the GAIN Trial (GingiPAIN inhibitor for treatment of Alzheimer’s disease) was a Phase 2/3 randomized, double-blind, placebo-controlled study that assessed the efficacy, safety, and tolerability of two dose levels of atuzaginstat oral capsules in subjects with mild to moderate Alzheimer’s disease.  Randomized participants entered a screening period of up to six weeks, a 48-week treatment period, and a completed a safety six-week follow-up .

The GAIN Trial enrolled 643 participants in the United States, France, Spain, Poland, United Kingdom, and Netherlands

Visit www.GAINtrial.com for more information.  

Do You or Someone You Love Have Alzheimer’s Disease?