Cognition Therapeutics Publishes Phase 2 Study Results of Zervimesine for Alzheimer's Disease in Alzheimer's & Dementia Journal

PITTSBURGH, July 21, 2025 (GLOBE NEWSWIRE) -- Cognition Therapeutics, Inc. , (the “Company” or “Cognition”) (NASDAQ: CGTX), a clinical-stage company developing drugs that treat neurodegenerative disorders, published results of a proteomics analysis from the Phase 2 ‘SEQUEL’ COG0202 Study of zervimesine (CT1812) in adults with mild-to-moderate Alzheimer's disease. The manuscript, titled Identification of Cerebrospinal Fluid Pharmacodynamic Biomarkers and Molecular Correlates of Brain Activity in a Phase 2 Clinical Trial of the Alzheimer's Disease Drug Candidate, CT1812 , was published in the peer-reviewed journal Alzheimer's & Dementia: Translational Research & Clinical Interventions. SEQUEL was a single-site study that investigated the effect of zervimesine on synaptic function using quantitative electroencephalography (qEEG), a noninvasive technique to measure electrical activity of the brain.

In the SEQUEL study ( NCT04735536 ), zervimesine treatment resulted in consistent trends of improvement across all prespecified EEG parameters, including the prominence of certain EEG frequencies associated with Alzheimer’s disease. Slower frequencies termed “theta” waves were reduced after 29 days of zervimesine treatment compared to placebo. This suggests zervimesine may normalize the function of neurons and synapses.

Additionally, zervimesine treatment was associated with an improvement in global alpha AEC-c, a measure of functional connectivity, suggesting zervimesine may be facilitating communication between brain regions. Analysis was performed to identify proteins associated with zervimesine’s normalizing effect on AEC-c. Proteins that were significantly altered with zervimesine treatment compared to placebo were associated with vesicle formation, exocytosis and endosomal trafficking. These key cellular functions allow neurons to recycle and eject cellular debris, and transport cargo needed for cellular function.

“These recycling and transport functions are necessary for the normal operation of any cell,” explained Mary Hamby, PhD, Cognition Therapeutics’ VP of research . “Our analysis from the SEQUEL study shows zervimesine has the ability to preserve the health and function of neurons that are under stress in Alzheimer’s disease. We delved into this neuroprotective function in a series of in vitro experiments that used an oxidative stressor to mimic neurodegenerative disease conditions. We showed zervimesine preserves the health and function of neurons - not only in cell culture but also in the brain of Alzheimer’s patients.”

In vitro studies were conducted using neurons derived from a human cell line. Neurons cultured in this way possess many of the functions of cells in the brain. They form long branches that make connections with neighboring cells, move cargo through cells, and recycle cell waste. They may also be damaged by the same toxic elements that drive neurodegenerative disease, such as oxidative stress, which contributes to disease progression. In this way, these cell cultures are useful models of disease states.

4-Hydroxynonenal (4-HNE) is a naturally occurring molecule known to induce oxidative stress. 4-HNE is found in high levels in the brains of people with neurodegenerative diseases. When added to a culture of neurons in this study, cells began to die as soon as four hours after exposure to 4-HNE. By 24 hours, more than 50% of the cells had died. This was evident not only by the visual appearance of the culture, but also by an increase in levels of a structural protein called neurofilament light (NfL) that was released from dying neurons into the culture medium. However, when zervimesine was added with the 4-HNE to the cultures, cell viability was preserved, and cellular levels of NfL were also maintained, attesting to the structural integrity of the neurons.

Further study showed zervimesine was able to preserve cell integrity and function in the face of a toxic compound such as 4-HNE by interrupting 4-HNE's ability to induce cell death.

Dr. Hamby concluded, “Cell death can be triggered through several processes, including apoptosis. Additional research will be needed to determine the precise point at which zervimesine prevents cell death under oxidative stress conditions. This neuroprotective mechanism may underlie the decrease in NfL that was observed in Alzheimer's patients treated with zervimesine in the 6-month ‘SHINE’ Study of mild-to-moderate Alzheimer's disease.”

These findings were presented at a recent Keystone Symposium and the posters are available on our website .

About Cognition Therapeutics, Inc.
Cognition Therapeutics, Inc. , is a clinical-stage biopharmaceutical company discovering and developing innovative, small molecule therapeutics targeting age-related degenerative disorders of the central nervous system. We recently completed Phase 2 studies of our lead candidate, zervimesine (CT1812) in dementia with Lewy bodies (DLB), mild-to-moderate Alzheimer’s disease and geographic atrophy secondary to dry AMD. The Phase 2 START study ( NCT05531656 ) in early Alzheimer’s disease is ongoing. We believe zervimesine can regulate pathways that are impaired in these diseases though its interaction with the sigma-2 receptor, a mechanism that is functionally distinct from other approaches for the treatment of degenerative diseases. More about Cognition Therapeutics and our pipeline can be found at https://cogrx.com .

About Zervimesine (CT1812)
Zervimesine (CT1812) is an investigational, oral, once-daily pill in development for the treatment of CNS diseases such as Alzheimer’s disease and dementia with Lewy bodies (DLB). While these diseases have different symptoms, both are associated with the buildup of certain proteins in the brain – Aβ and ɑ-synuclein. As these proteins bind to neurons, they can damage and ultimately destroy the neurons. This results in a progressive loss in a person’s ability to learn, recall memories, move efficiently, or communicate. These diseases progress relentlessly and ultimately result in death. If zervimesine can interrupt the toxic effects of these proteins, it may be able to slow progression of disease and improve the lives of those suffering from Alzheimer’s and DLB. Zervimesine has been generally well tolerated in clinical studies to date. Zervimesine has been granted FDA Fast Track designation in Alzheimer’s disease.

The USAN Council has adopted zervimesine as the United States Adopted Name (USAN) for CT1812.

About the SEQUEL Study
The SEQUEL study ( NCT04735536 ) enrolled 16 adults (15 of whom completed the study) with mild-to-moderate Alzheimer’s disease (MMSE 18-26), each of whom were randomized to receive either 300mg CT1812 or placebo once daily for 29 days. After a 14-day wash-out period, participants cross over into the other treatment arm for an additional 29 days. Quantitative EEG evaluations were taken periodically throughout the duration of the trial. SEQUEL was designed to assess the safety and efficacy of CT1812 and to measure the impact of CT1812 on the electrical activity in the brain, specifically those electrical impulses in the theta band.

SEQUEL was supported by $5.3 million in grant awards (R01AG058710) by the National Institute of Aging (NIA) of the National Institutes of Health (NIH).

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this press release or made during the conference, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding our product candidates, including zervimesine (CT1812), and any expected or implied benefits or results, including that initial clinical results observed with respect to zervimesine will be replicated in later trials and our clinical development plans, including statements regarding our clinical studies of zervimesine and any analyses of the results therefrom, are forward-looking statements. These statements, including statements relating to the timing and expected results of our clinical trials involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: competition; our ability to secure new (and retain existing) grant funding; our ability to grow and manage growth, maintain relationships with suppliers and retain our management and key employees; our ability to successfully advance our current and future product candidates through development activities, preclinical studies and clinical trials and costs related thereto; uncertainties inherent in the results of preliminary data, pre-clinical studies and earlier-stage clinical trials being predictive of the results of early or later-stage clinical trials; the timing, scope and likelihood of regulatory filings and approvals, including regulatory approval of our product candidates; changes in applicable laws or regulations; the possibility that the we may be adversely affected by other economic, business or competitive factors, including ongoing economic uncertainty; our estimates of expenses and profitability; the evolution of the markets in which we compete; our ability to implement our strategic initiatives and continue to innovate our existing products; our ability to defend our intellectual property; the impacts of ongoing global and regional conflicts on our business, supply chain and labor force; our ability to maintain the listing of our common stock on the Nasdaq Global Market; and the risks and uncertainties described more fully in the “Risk Factors” section of our annual and quarterly reports filed with the Securities & Exchange Commission and are available at www.sec.gov . These risks are not exhaustive and we face both known and unknown risks. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

This press release was published by a CLEAR® Verified individual.