Zervimesine Demonstrates Symptom Slowing in Phase 2 SHIMMER Trial for Dementia With Lewy Bodies

A phase 2 analysis of zervimesine (CT1812; Cognition Therapeutics) in mild to moderate dementia with Lewy bodies (DLB) suggests that the investigational oral sigma-2 receptor modulator may slow disease progression across multiple symptom domains — including neuropsychiatric, cognitive, motor, and functional outcomes — with a favorable safety and tolerability profile.¹ The findings, presented at the 2026 AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, held March 17-21 in Copenhagen, Denmark, came from the phase 2 SHIMMER clinical trial (NCT05225415).

Trial Design and Population

The SHIMMER study was a multicenter, double-blind, placebo-controlled, parallel-group phase 2 trial enrolling 130 adults aged 50 to 85 years with probable DLB, a Mini-Mental State Examination (MMSE) score of 18 to 27, and without neurological comorbidities. Participants were randomized 2:1 to once-daily oral zervimesine at 100 mg or 300 mg or placebo for 26 weeks, with a total of 88 participants in the two active treatment arms and 42 in the placebo arm. The primary end point was safety and tolerability; the trial was not powered to demonstrate efficacy. Exploratory efficacy end points spanned neuropsychiatric, cognitive, motor, and functional domains.

Key Efficacy Findings

Across the full population of treated participants, those in the zervimesine arms progressed more slowly than those on placebo on all exploratory efficacy assessments. Neuropsychiatric outcomes measured by the Neuropsychiatric Inventory (NPI-12) — which captures frequency and severity of 12 behavioral symptoms — showed 86% slowing of decline relative to placebo (P = .0545) for the full NPI-12 scale. Core DLB symptoms that improved relative to placebo included hallucinations (P = .0207), anxiety (P = .0082), and delusions (P = .0609). NPI Caregiver Distress scores showed a 115% improvement versus placebo on the full NPI-12 scale (P = .0254), with significant between-group differences noted for hallucinations (P = .0048) and anxiety (P = .0174).

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Within the cognitive domain, assessments using the Cognitive Drug Research (CDR) Battery showed statistically significant signals on Immediate Word Recall (P = .0279), Word Recognition (P = .0081), and Picture Recognition (P = .0148). On the Alzheimer's Disease Cooperative Study – Activities of Daily Living (ADCS-ADL), zervimesine demonstrated 52% preservation of daily functioning relative to placebo (P = .0503). The Montreal Cognitive Assessment (MoCA) and Movement Disorder Society – Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) results were also in the directionally favorable direction for the treatment group, though specific P values for those outcomes were not reported in the abstract.

The SHIMMER study met its primary end point: the study confirmed zervimesine's safety and tolerability, and zervimesine was also shown to have a favorable impact on behavioral, cognitive, functional, and movement domains, many of which are core clinical features of DLB.

Regulatory Trajectory for DLB

Following the SHIMMER publication, Cognition Therapeutics conducted a Type C meeting with the FDA on January 21, 2026, with the objective of reviewing plans for the proposed Phase 2b study of zervimesine in DLB — a disease with no FDA-approved therapies — focusing on clinically meaningful endpoints.² In March 2026, after receipt of final FDA meeting minutes, Cognition announced it would advance zervimesine into a registrational program specifically for DLB psychosis, given the strength of the SHIMMER neuropsychiatric and behavioral signal. The next study will focus on measurement of neuropsychiatric symptoms such as hallucinations and delusions, and behavioral symptoms such as anxiety, aggression, and agitation, using established validated endpoints, with participants randomized to 100 mg of oral zervimesine or placebo daily, followed by an open-label extension. Cognition has indicated it plans to meet with the FDA's Division of Psychiatry by mid-2026 to discuss the DLB psychosis registrational program.²

In parallel, an expanded access program (EAP; COG1202) has been enrolling adults with DLB since June 2025, with 32 participants across 8 US sites receiving 100 mg of oral zervimesine daily; the EAP was extended in February 2026 to allow several additional months of treatment beyond the original 12-month duration.³

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REFERENCES
1. Grundman M, Galvin J, Iaci J,Caggiano A. Zervimesine slows progression of symptoms in mild to moderate DLB. Alzheimer's Dement. 2025;21:e71004. Presented at: AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, March 17-21, 2026; Copenhagen, DE. Abstract #2640
2. Cognition Therapeutics, Inc. Cognition Therapeutics Completes Type C Meeting with FDA for Zervimesine (CT1812) in Dementia with Lewy Bodies. Press release. January 27, 2026. https://ir.cogrx.com/press_releases/cognition-therapeutics-completes-type-c-meeting-with-fda-for-zervimesine-ct1812-in-dementia-with-lewy-bodies/
3. Cognition Therapeutics, Inc. Cognition Therapeutics Extends Expanded Access Program for Zervimesine (CT1812) in Dementia with Lewy Bodies. Press release. February 5, 2026. https://www.globenewswire.com/news-release/2026/02/05/3232883/0/en/Cognition-Therapeutics-Extends-Expanded-Access-Program-for-Zervimesine-CT1812-in-Dementia-with-Lewy-Bodies.html