Zervimesine May Slow Progression of Dementia With Lewy Bodies, Phase 2 Results Show

Cognition Therapeutics announced positive phase 2 results of the SHIMMER study, with zervimesine meeting primary endpoints and showing favorable results in clinical features of dementia with Lewy bodies.¹

“The Phase 2 SHIMMER study, our first in [dementia with Lewy bodies], met its primary goal of confirming zervimesine’s safety and tolerability,” said Anthony O. Caggiano, MD, PhD, chief medical officer of Cognition Therapeutics, in a press release.¹ "Importantly, zervimesine was also shown to have a favorable impact on behavioral, cognitive, functional, and movement domains, many of which are core clinical features of [dementia with Lewy bodies]. There are currently no approved disease-modifying treatments for [dementia with Lewy bodies], highlighting the unmet need for novel therapies,” he added.

The phase 2 SHIMMER study was a randomized, placebo-controlled trial including 130 adults aged 50 to 85 years with mild to moderate dementia with Lewy bodies.² Patients received a daily oral dose of zervimesine 100 mg or 300 mg or placebo for a treatment period of 6 months. Assessments of the Neuropsychiatric Inventory (NPI), Clinician Assessment of Fluctuation (CAF), Montral Cognitive Assessment, Cognitive Drug Research Battery, and the MDS-Unified Parkinson’s Disease Rating Scale. Participants were screened for intervening neurological disease or clinical events like stroke or head trauma, and underwent genotype screening for apolipoprotein E. Participants taking acetylcholinesterase inhibitors, mematine, or a combination were on a stable dose for at least 12 weeks prior to screening, with no plans for dose adjument during the study period. Mean age of all participants was 72.8 years, with the total group 81.5% male and 91.5% white, and mean time since probable diagnosis of dementia with Lewy bodies was 2 years.

Primary endpoints for safety and tolerability of zervimesine were met in this study. After 6 months, patients who received zervimesine showed improved symptoms as measured by the neuropsychiatric inventory. The inventory measured symptoms like hallucinations, delusions, anxiety, and agitation, which are hallmarks for dementia with Lewy bodies and can be debilitating. Participants receiving zervimesine also showed an improvement in fluctuations, which were defined as unpredictable lapses in attention or consciousness for minutes to days. Individuals in the treatment group also showed improvement in activities of daily living such as dressing, bathing, and writing.

Zervimesine (CT1812) is a sigma-2 receptor modulator that blocks binding and displaces A-beta and alpha-synuclein oligomers from receptor sites to preserve neuronal synapses and normalize neural functioning.² In previous preclinical studies, zervimesine was shown to antagonize binding of A-beta oligomers to neuronal synapses, protect neuronal synapses, and restore membrane trafficking deficits cause by A-beta oligomers.³

The US Food and Drug Administration will meet with the pharmaceutical company for a type C meeting in the second half of January. The meeting will focus on future clinical studies for zervimesine in dementia with Lewy bodies, and meeting minutes are expected to be released afterwards.

References

1. Cognition Therapeutics publishes phase 2 clinical results showing zervimesine’s potential to slow the progression of dementia with Lewy bodies. Press release. January 6, 2026. Accessed January 6, 2026. https://www.globenewswire.com/news-release/2026/01/06/3213500/0/en/Cognition-Therapeutics-Publishes-Phase-2-Clinical-Results-Showing-Zervimesine-s-Potential-to-Slow-the-Progression-of-Dementia-with-Lewy-Bodies.html

2. Galvin JE, Tolea MI, Scharre DW, et al. Phase 2 study of zervimesine (CT1812) in participants with mild-to-moderate dementia with Lewy bodies (DLB). Alzheimer's Dement. 2025; 21:e71004.

3. Limegrover CS, LeVine H 3rd, Izzo NJ, et al. Alzheimer's protection effect of A673T mutation may be driven by lower Aβ oligomer binding affinity. J Neurochem. 2021;157(4):1316-1330.