Cognition Therapeutics Presents Data at AAIC Highlighting Broad Neurological Impact of Zervimesine (CT1812) in Dementia with Lewy Bodies and Alzheimer’s Disease

Rhea-AI Summary

Cognition Therapeutics (NASDAQ: CGTX) presented significant clinical data for their drug zervimesine (CT1812) at AAIC 2025, demonstrating positive results in both Dementia with Lewy Bodies (DLB) and Alzheimer's disease trials.

In the Phase 2 SHIMMER study, DLB patients treated with zervimesine showed 86% better scores than placebo on neuropsychiatric symptoms. The Phase 2 SHINE study in Alzheimer's revealed that patients with lower p-tau217 levels showed remarkable response, with cognitive deterioration arrested by 129% in mild cases and 91% in moderate cases.

Additional biomarker analyses showed significant reductions in plasma GFAP and promising trends in NfL and amyloid beta species, indicating zervimesine's impact on underlying disease biology.

Insights

Neuropharmacology Specialist

Zervimesine shows promising efficacy in DLB and Alzheimer's, with biomarker data supporting its mechanism of action and potential targeted patient selection.

Cognition Therapeutics has reported significant clinical data for their lead compound zervimesine (CT1812) across two Phase 2 trials. The SHIMMER study in dementia with Lewy bodies (DLB) demonstrated not just safety, but meaningful clinical impact - with treated patients scoring 86% better than placebo on the neuropsychiatric inventory (NPI-12). This is particularly notable for addressing hallucinations, delusions, and anxiety - symptoms that are extremely challenging to treat in DLB patients who often react poorly to conventional neuropsychiatric medications.

The data from the SHINE trial in Alzheimer's disease provides even more compelling insights into the drug's potential. The identification of p-tau217 as a predictive biomarker represents a critical advancement, essentially creating a precision medicine approach for Alzheimer's treatment. Patients with lower p-tau217 levels showed remarkable response, with cognitive deterioration arrested by 129% in mild disease and 91% in moderate disease. This ability to identify likely responders through a simple blood test could dramatically improve treatment efficiency.

The biomarker data further supports zervimesine's mechanism of action, showing reductions in GFAP (a neuroinflammation marker) and trends toward normalizing neurofilament light and amyloid beta species. These biomarker changes align with the drug's proposed mechanism of targeting σ-2 receptors to restore synaptic function and reduce neuroinflammation. Overall, these results suggest zervimesine could represent a meaningful advance in treating both DLB and Alzheimer's disease, with a predictable patient response profile.

Clinical Neurologist

The SHIMMER trial results represent a potentially significant breakthrough in DLB treatment. The 86% improvement over placebo on the NPI-12 scale addresses precisely the symptoms that most devastate quality of life - hallucinations, delusions, and anxiety. For context, current DLB management is severely limited, as antipsychotics can trigger life-threatening sensitivity reactions, while cholinesterase inhibitors provide only modest symptomatic benefit.

The SHINE trial's Alzheimer's data introduces a critical precision medicine component through p-tau217 stratification. The cognitive decline arrested by 129% in mild and 91% in moderate Alzheimer's patients with lower p-tau217 levels suggests we may be able to identify ideal candidates for zervimesine therapy. This represents a significant advance over current treatment approaches that broadly target symptoms without biomarker guidance.

The biomarker findings further substantiate zervimesine's biological activity, showing effects on neuroinflammation (GFAP reduction), neurodegeneration (NfL trends), and amyloid processing. These consistent changes across both CSF and plasma biomarkers strengthen the evidence that zervimesine is modifying disease biology rather than simply masking symptoms. The convergence of symptomatic improvement with biomarker changes is particularly encouraging, as it suggests zervimesine may be addressing fundamental disease processes in both DLB and Alzheimer's. If these results are maintained in larger Phase 3 studies, zervimesine could represent a significant advancement in neurodegeneration treatment.

- Zervimesine’s impact on debilitating DLB behavioral symptoms highlighted in podium presentation -
- Plasma p-tau217 levels can identify Alzheimer’s patients most likely to benefit from zervimesine treatment -
- Plasma and CSF biomarkers support zervimesine’s impact on Alzheimer’s disease biology -

PURCHASE, N.Y., July 29, 2025 (GLOBE NEWSWIRE) -- Cognition Therapeutics, Inc., (the Company or Cognition) (NASDAQ: CGTX), a clinical stage company developing drugs that treat neurodegenerative disorders, presented results from the Phase 2 COG1201 SHIMMER study (NCT05225415) of zervimesine (CT1812) in dementia with Lewy bodies (DLB) at the Alzheimer’s Association International Conference (AAIC 2025).

As previously reported, the SHIMMER study met its primary endpoint of safety and tolerability. Results showed that zervimesine treatment had a positive impact across neuropsychiatric, cognitive, motor, and functional scales. After six months of treatment, DLB patients treated with zervimesine scored an average of 86% better than placebo-treated patients on the neuropsychiatric inventory (NPI-12). This tool measures 12 separate behavioral symptoms, including hallucinations, delusions, and anxiety, which are hallmarks of DLB. The findings were presented by James E. Galvin, MD, MPH during a Featured Research Session on July 29, 2025.

“Among the NPI-12 components, hallucinations, delusions, and anxiety are often considered most troubling to patients and their care partners,” stated Dr. Galvin, director of the Comprehensive Center for Brain Health at the University of Miami Miller School of Medicine and the SHIMMER study director. “These behavioral symptoms are also some of the most challenging to treat, since DLB patients have severe and sometimes dangerous reactions to many commonly used neuropsychiatric drugs. This made zervimesine’s impact even more notable.”

Results from the Phase 2 COG0201 ‘SHINE’ study (NCT03507790) of zervimesine in Alzheimer’s disease were also presented at AAIC. The SHINE study met its primary endpoint of safety and tolerability. An analysis was conducted on a subgroup of participants whose Alzheimer’s disease brain pathology was less pronounced, as determined by lower levels of a protein called p-tau217 in their blood. Approximately half of this subgroup was identified as having mild Alzheimer’s disease and half with moderate Alzheimer’s disease by the mini mental state exam (MMSE). The MMSE is a standard test that measures memory, attention, language and other functions to evaluate the degree of a person’s cognitive impairment.

SHINE participants with lower p-tau217 had a more robust response to zervimesine compared to those with higher p-tau217 levels regardless of their MMSE scores. Zervimesine was shown to arrest further cognitive deterioration in people with mild or moderate Alzheimer’s disease by 129% and 91%, respectively. Anthony Caggiano, MD, PhD, Cognition’s CMO and head of R&D, explained, “This was an important finding as we now know we can identify patients who are more likely to benefit from zervimesine treatment through a simple blood test for p-tau217.”

Additionally, two research posters delve into the mechanism that underlies the impact of zervimesine in Alzheimer’s disease. These posters summarize analyses of the cerebrospinal fluid (CSF) and plasma biomarkers from SHINE participants with lower levels of p-tau217. In these individuals, significant reductions were observed in the level of plasma glial fibrillary acidic protein (GFAP), a protein associated with neuroinflammation. In addition, there were trends towards the normalization of neurofilament light (NfL), a protein associated with neurodegeneration, and amyloid beta species (Aβ40 and 42).

“The biomarker evidence we’re presenting at AAIC shows that zervimesine treatment had an effect on proteins involved in neuroinflammation, synapse health and neurodegeneration,” added Mary Hamby, PhD, VP of research. “This is consistent with previously reported results showing significant decreases in NfL and normalizing trends in amyloid beta species in the CSF of people treated with zervimesine. This is encouraging evidence that zervimesine is impacting the underlying Alzheimer’s disease biology.”

Dr. Galvin’s slide presentation and Cognition’s three posters will be available on the Cognition Therapeutics website in accordance with the conference’s embargo policy.

About the SHIMMER Study in Dementia with Lewy Bodies
The SHIMMER study (COG1201; NCT05225415) is an exploratory double-blind, placebo-controlled Phase 2 clinical trial that enrolled 130 adults with mild-to-moderate DLB, who were randomized to either daily oral doses of zervimesine (100 mg or 300 mg) or placebo for six months. A total of 88 participants were randomized to the two treatment arms and 42 to the placebo arm. Assessments were conducted throughout the study using a number of tools, including the Neuropsychiatric Inventory (NPI) to measure changes in hallucinations, anxiety and delusions; the Clinician Assessment of Fluctuation (CAF) to measure the frequency and duration of cognitive fluctuations; the Montreal Cognitive Assessment (MoCA) and Cognitive Drug Research Battery (CDR), which track cognitive performance; and the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, an objective assessment of parkinsonism.

The SHIMMER study is supported by a grant award from the National Institute on Aging of the National Institutes of Health (NIH) totaling approximately $30 million (R01AG071643) and was conducted in collaboration with James E. Galvin, MD, MPH, director of the Comprehensive Center for Brain Health at the University of Miami Miller School of Medicine and the Lewy Body Dementia Association (LBDA).

About the SHINE Study in Mild-to-Moderate Alzheimer’s Disease
The SHINE study (NCT03507790) is a double-blind, placebo-controlled Phase 2 signal-finding trial that enrolled 153 adults with mild-to-moderate Alzheimer’s disease who were evenly randomized to receive either placebo or one of two doses of CT1812 (100 mg or 300 mg), which was taken orally daily for six months. The primary endpoint was safety and tolerability. The key secondary endpoint of cognition was ADAS-Cog 11. Exploratory endpoints included change in MMSE, ADAS-Cog 13, ADCS-ADL and -CGIC as well as pre-specified subgroup analyses included a comparison of cognitive and functional changes in participants with plasma p-tau217 levels above and below the median.

The SHINE study was supported by two grant awards from the National Institute on Aging of the National Institutes of Health (NIH) totaling approximately $30 million.

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 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 and retina. We currently are investigating our lead candidate, zervimesine (CT1812), in clinical programs in dementia with Lewy bodies (DLB) and Alzheimer’s disease, including the ongoing START study (NCT05531656) in early Alzheimer’s disease. We believe zervimesine and our pipeline of σ-2 receptor modulators can regulate pathways that are impaired in these diseases that are 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.

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 future clinical development plans, and statements regarding our clinical trials 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 Capital 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.

Contact Information: Cognition Therapeutics, Inc. info@cogrx.com	Casey McDonald (media) Tiberend Strategic Advisors, Inc. cmcdonald@tiberend.com	Mike Moyer (investors) LifeSci Advisors mmoyer@lifesciadvisors.com

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FAQ

What were the key results of Cognition Therapeutics' (CGTX) SHIMMER trial for DLB?

The Phase 2 SHIMMER trial met its safety endpoint and showed that DLB patients treated with zervimesine scored 86% better than placebo on the neuropsychiatric inventory (NPI-12), which measures behavioral symptoms including hallucinations and anxiety.

How effective was zervimesine (CT1812) in treating Alzheimer's disease in the SHINE study?

In patients with lower p-tau217 levels, zervimesine arrested cognitive deterioration by 129% in mild Alzheimer's and 91% in moderate Alzheimer's cases.

What biomarkers showed improvement in CGTX's Alzheimer's trial?

The trial showed significant reductions in plasma GFAP (neuroinflammation marker) and positive trends in neurofilament light (NfL) and amyloid beta species (Aβ40 and 42).

How can doctors identify which patients might respond best to zervimesine treatment?

Doctors can use a simple blood test measuring p-tau217 levels to identify patients who are more likely to benefit from zervimesine treatment.

What types of symptoms does zervimesine target in DLB patients?

Zervimesine targets neuropsychiatric symptoms including hallucinations, delusions, and anxiety, which are particularly challenging to treat in DLB patients due to their sensitivity to common neuropsychiatric drugs.