July 19, 2019
“In Phase 1a/b testing, COR388 was well tolerated and associated with encouraging signs of early clinical activity, providing a solid rationale for the GAIN trial, our ongoing Phase 2/3 study that seeks to enroll approximately 570 patients with mild to moderate Alzheimer’s disease,” said Michael Detke, M.D., Ph.D., Cortexyme’s chief medical officer. “The response from the Alzheimer’s investigator and patient communities has been strong, and we look forward to enrolling the study and fully evaluating COR388’s utility as a potential treatment for Alzheimer’s.”
GAIN Trial’s Scientific Foundation and Clinical Trial Design Detailed
In a Developing Topics poster (P4-663), researchers detailed the rationale for and design of the GAIN trial, which began enrolling subjects in the United States in April 2019. The trial represents the first large, randomized late-stage clinical study evaluating the gingipain hypothesis, which is based upon growing evidence that the bacterium most commonly associated with chronic periodontal disease, Porphyromonas gingivalis, plays a key role in the development of AD, given its identification in the brains of AD patients and ability to cause neurodegeneration, inflammation, and other pathology associated with Alzheimer’s in animal models. In these models, the pathological effects were blocked by COR388, which targets the gingipains, or toxic proteases, released by P. gingivalis as it colonizes tissue.
The GAIN trial is based on Phase 1b data demonstrating benefits on both biomarkers and cognitive endpoints. After a 10-day multiple ascending dose study in 24 older healthy volunteers showed an encouraging tolerability and safety profile, a 28-day study of nine subjects with mild to moderate AD between the ages of 55 and 85 was conducted. Participants showed a trend to improvement on several measures of cognition, including the Mini-Mental State Exam (MMSE) and Cambridge Neuropsychological Test Automated Battery (CANTAB) memory composite of cognitive function score, measures commonly used to assess cognitive impairment in Alzheimer’s patients. Researchers also reported a statistically significant improvement for COR388 versus placebo on multiple measures of the Winterlight Cognitive Assessment, a new speech-based testing platform intended to identify cognitive impairment associated with dementia. Across the Phase 1b study, as well as single and multiple ascending dose studies in healthy volunteers, COR388 twice daily was found to be well tolerated and brain penetrant.
As part of an AAIC news briefing earlier this morning, lead author Michael Detke, M.D., Ph.D. shared data from the patient cohort demonstrating a reduction in markers of inflammation in the blood (plasma RANTES), as well as a reduction in pathological ApoE fragments in the cerebrospinal fluid (CSF), which suggests another potential benefit of inhibiting gingipain activity in the brains of patients.
“COR388 has been shown to block ApoE fragmentation in in vitro, and, as seen at AAIC today, human studies,” said Michael Detke. “We believe this makes COR388 the first investigational small molecule to show beneficial effects related to pathological fragmentation of ApoE, the most common genetic risk factor for Alzheimer’s. More research is needed, but the data generated to date suggests another avenue by which Porphyromonas gingivalis is implicated in Alzheimer’s pathogenesis.”
Spurred by the totality of data from Phase 1a/b testing, investigators are now enrolling subjects in the GAIN trial, which is targeting an enrollment of up to 570 patients with mild to moderate AD at ~90 sites in the United States and Europe. Participants are randomized to one of two doses of COR388 capsules (40mg or 80mg twice daily) or placebo. The primary endpoint of the study is the mean change in the Alzheimer’s disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11), a measure that has supported past regulatory approval of drugs to treat Alzheimer’s disease, along with secondary endpoints of function ADCS-ADL and CDR-SB. Cortexyme has developed a sensitive assay for Porphyromonas gingivalis DNA in the central nervous system, and biomarkers of the infection in the saliva, blood and CSF are being closely tracked for responder analyses. Top-line results from the GAIN trial are expected by the end of 2021.
About Cortexyme, Inc.
Cortexyme (Nasdaq: CRTX) is a clinical stage biopharmaceutical company pioneering a novel disease-modifying therapeutic approach to treat a key underlying cause of Alzheimer’s disease and other degenerative diseases. Cortexyme is targeting a specific, infectious pathogen found in the brain of Alzheimer’s patients and tied to neurodegeneration and neuroinflammation in animal models. The company’s lead investigational medicine, COR388, is the subject of the GAIN trial, an ongoing Phase 2/3 clinical study in patients with mild to moderate Alzheimer’s disease. More information about the trial can be found at www.GAINtrial.com. To learn more about Cortexyme, visit www.cortexyme.com.
Statements in this press release contain “forward-looking statements” that are subject to substantial risks and uncertainties. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “expect,” “believe,” “will,” “may,” “should,” “estimate,” “project,” “outlook,” “forecast” or other similar words. Forward-looking statements are based on Cortexyme’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. Factors that could cause actual results to differ include, but are not limited to, the risks and uncertainties described in the section titled “Risk Factors” in the final prospectus related to Cortexyme’s initial public offering filed with the Securities and Exchange Commission on May 9, 2019 and Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on June 12, 2019. Forward-looking statements contained in this press release are made as of this date, and Cortexyme undertakes no duty to update such information except as required under applicable law.
For Cortexyme, Inc.