Additional foreground data presented at CTAD 2021
Evidence supports P. gingivalis as a driver of Alzheimer’s disease in an easily identifiable patient population
Successful identification of target population and therapeutic dose informs next steps
SOUTH SAN FRANCISCO, California, November 11, 2021– (BUSINESS WIRE) – Cortexyme, Inc. (Nasdaq: CRTX) to present additional data from its Phase 2/3 GAIN trial at the 14e Alzheimer’s Disease Clinical Trials Conference (CTAD 2021) as part of the Last Minute Reading Roundtable Program of the meeting today, Thursday, November 11, 2021 at 11:35 a.m. EST, to be held in Boston, Massachusetts, as well as virtually. The presentation will expand on the first results previously reported which demonstrated the relationship between the reduction of Porphyromonas gingivalis (P. gingivalis) infection and slowing of cognitive decline in Alzheimer’s disease with treatment with atuzaginstat in a predefined patient population based on the diagnosis of infection.
The 48-Week GAIN Trial with 643 Participants Was the First Large Study to Test the Effectiveness of Oral Small Molecule Targeting P. gingivalis for disease modification in patients with mild to moderate Alzheimer’s disease. Although not statistically significant on its primary cognitive and functional endpoints across the cohort, study data showed that treatment with atuzaginstat slowed the decline compared to placebo in the majority of clinical endpoints in predefined populations that were selected on the basis of P. gingivalis markers of infection.
The results of the GAIN trial showed that the 40 mg BID arm demonstrated equivalent or better efficacy on key endpoints compared to the highest dose, 80 mg BID, as well as a safety profile. superior. Profit trends at 40 mg BID were observed with several predefined analytical approaches, including ADAS-Cog11, CDR-SB, MMSE and NPI, with increasing separation from placebo throughout the study consistent with a modification of disease. No benefit was seen with ADCS-ADL at either dose. Changes in P. gingivalis DNA levels in saliva were significantly correlated with clinical outcomes during and at the end of treatment, demonstrating that the reduction P. gingivalis the bacterial load led to better clinical outcomes. A slowing trend in the primary endpoint of the hippocampal atrophy biomarker was observed in the treatment groups, but did not reach significance.
“Our ability to identify the right population in patients with historically difficult-to-treat mild to moderate Alzheimer’s disease, as well as to find an effective dose with a differentiated safety profile, is an important advance towards a breakthrough treatment for Alzheimer’s disease, “said Michael Detke, MD, PhD, chief medical officer of Cortexyme. âWe have seen clinically significant effects ranging from 30% to 50% slowing down on ADAS-Cog11 and CDR-SB measurements. The benefits on these widely accepted scales provide an informative basis for a confirmatory study. This landmark study significantly advances our understanding of P. gingivalis as an upstream driver of Alzheimer’s disease progression, and we look forward to sharing additional study data as it becomes available in the coming months. “
âThe GAIN trial made several significant advances in the field of Alzheimer’s disease, first of all by clinically confirming that P. gingivalis is a key factor upstream of the progression of the disease. In addition, the data demonstrated a compelling risk-benefit profile with a clinically significant response to treatment in an easily identifiable patient population, âsaid Marwan Sabbagh, MD, FAAN, principal investigator of the GAIN trial and professor of neurology at the Barrow Neurological Institute. âI am particularly encouraged by GAIN’s identification of a target population, which is consistent with the heterogeneous nature of Alzheimer’s disease and comparable to therapeutic advances based on the diagnosis of infectious diseases, such as HIV dementia and medicine. customization common in other therapeutic areas, such as oncology. When combined with the convenience of oral administration, atuzaginstat offers the potential to fill a huge gap in the underserved population with mild to moderate Alzheimer’s disease in up to half of these patients. I was delighted to act as the principal investigator for this important study which will hopefully become part of our arsenal of treatments for Alzheimer’s disease in the not-so-distant future. “
For all critical safety measures, levels in the 40 mg twice daily treatment arm were either comparable to placebo or significantly better than in the 80 mg twice daily arm. Most of the adverse events were mild to moderate in intensity. The most common were gastrointestinal, such as diarrhea in up to 16% and nausea in 6% of participants treated with atuzaginstat, compared with 3% and 2% of participants on placebo, respectively. Atuzaginstat was associated with dose-related elevations in liver enzymes> 3 times upper limit of normal: 2% on placebo, 7% on 40 mg twice daily and 15% on 80 mg twice daily . These elevations alone were not clinically significant and virtually all participants were asymptomatic. Two participants in the 80 mg BID arm had concomitant elevations in bilirubin without further explanation. The lab changes resolved while participants continued to take the drug or after withdrawal without any known long-term side effects. The groups treated with Atuzaginstat showed no increase in ARIA (amyloid-related imaging abnormalities), including microhaemorrhages and edema, or superficial siderosis.
âThe data generated by this unique study adds an important new dimension to our understanding of Alzheimer’s disease,â said Casey Lynch, CEO, co-founder and president of Cortexyme. âThe study was successful in achieving many of our goals, including identifying the appropriate population for treatment and therapeutic dose. We intend to apply our lessons to advance an early confirmation study, pending discussions with the FDA and global regulators.
Access Cortexyme’s last minute roundtable at CTAD 2021
The last-minute Cortexyme Reading Roundtable presentation at CTAD 2021 will be available today, Thursday, November 11, 2021, starting at 11:35 a.m. EST, through the Investor Relations website of the company at ir.cortexyme.com, in addition to being accessible to CTAD. participants registered for the meeting in person and on its virtual platform.
Cortexyme, Inc. (Nasdaq: CRTX) is a clinical-stage biopharmaceutical company pioneering upstream therapeutic approaches designed to improve the lives of patients diagnosed with Alzheimer’s disease and other degenerative diseases. Cortexyme’s main program targets a specific infectious pathogen called P. gingivalis found in the brains of Alzheimer’s disease patients and other organs and linked to degeneration and inflammation in humans and animal models. The company’s causal evidence for Alzheimer’s disease and the mechanism of its new therapy has been independently replicated and confirmed by several laboratories around the world, as well as published in peer-reviewed scientific journals. To learn more about Cortexyme, visit www.cortexyme.com or follow @Cortexyme on Twitter.
The statements contained in this press release contain “forward-looking statements” which 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”, “could”, “should”, “estimate” , “Project,” “outlook”, “forecast”, “potential” or other similar terms. Examples of forward-looking statements include, among others, atuzaginstat’s strategic development path, its business plans, its strategy , planned clinical trials and its timeline, outlook and milestone expectations; the timing and success of the Company’s clinical trials and related data, including plans and ability to conduct a confirmatory study regarding the GAIN trial; the potential of atuzaginstat to treat Alzheimer’s disease; the timing of announcements and updates relating to its clinical trials and associated data; potential therapeutic benefits, safety and the eff efficiency of the product candidate or the company’s compound library and statements about its ability to obtain, and the timeline for further development of atuzaginstat, regulatory submissions and interactions with regulators, and related responses and decisions , including with respect to the Company’s partial clinical suspension, and approvals for the Company’s drug candidate. Forward-looking statements are based on Cortexyme’s current expectations and are subject to inherent uncertainties, risks and assumptions which are difficult to predict and could cause actual results to differ materially from what the company expects. In addition, certain forward-looking statements are based on assumptions about future events which may not prove to be correct. Factors that could cause actual results to differ include, but are not limited to, the risks and uncertainties described in the section entitled âRisk Factorsâ of Cortexyme’s Annual Report on Form 10-K filed with the Securities and Exchange. Commission (SEC) in March. 1, 2021, its quarterly report on Form 10-Q filed with the SEC on October 29, 2021, and other reports filed with the SEC. The forward-looking statements contained in this press release are made as of this date, and Cortexyme assumes no obligation to update such information, except as required by applicable law.
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