Elayta (zervimesine) / Cognition Therap - LARVOL DELTA

Crystal Structure of the Sigma‑2 Receptor Complexed with Investigational Drug Zervimesine (CT1812). (PubMed, ACS Med Chem Lett) - P2 | "The crystal structure of S2R complexed with zervimesine to 2.74 Å resolution reveals this investigational therapeutic bound in the binding site of S2R analogous to that seen previously with other S2R ligands, and is consistent with binding affinity data from a S2R competition assay. The structural interactions by which zervimesine binds with S2R are illuminated, which may shed light on the potential structure-function relationship underlying the favorable effects of zervimesine seen preclinically and clinically, and may foster the design of future S2R modulators for neurodegenerative conditions."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Dry Age-related Macular Degeneration • Lewy Body Disease

CT1812 Attenuates Surgery-Induced Cognitive Impairment and Modulates TMEM97- and PGRMC1-Associated Hippocampal Stress Responses in Aged Mice. (PubMed, Neurochem Res) - "In parallel, CT1812 attenuated a selective endoplasmic reticulum (ER) stress response involving binding immunoglobulin protein (BIP) and protein kinase R-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (eIF2α) signaling in hippocampal neurons, and suppressed microglial nuclear factor κB (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory activation, whereas C/EBP homologous protein (CHOP) was not significantly changed. These findings support a model in which postoperative injury in the aged hippocampus engages a lipid-proteostatic and inflammatory stress program associated with TMEM97 and PGRMC1, and suggest that CT1812 attenuates cognitive vulnerability by restraining this coupled response."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Dyslipidemia • Metabolic Disorders • Psychiatry • ABCA1 • APOE • CYP46A1 • DLG4 • GFAP • HSPA5 • NLRP3 • PERK • PLIN2 • SYP

TMEM97 links endoplasmic reticulum stress to hepatic stellate cell activation in experimental liver fibrosis: pharmacological attenuation by CT1812. (PubMed, Eur J Pharmacol) - "Human LX-2 cells were stimulated with transforming growth factor-β1 (TGF-β1) and treated with TMEM97-targeting small interfering RNA (siTMEM97), CT1812, or both; confirmatory experiments used a second siRNA and GSK2606414. In vivo, CT1812 reduced hepatic hydroxyproline accumulation, collagen staining, α-SMA and collagen I expression, ER-stress markers, liver-injury indices, inflammatory cytokines, and macrophage accumulation. These findings support TMEM97-associated σ-2 receptor complex signaling as a contributor to ER-stress-coupled HSC activation and identify CT1812 as a candidate pharmacological modulator of experimental liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • ACTA2 • ATF4 • ATF6 • COL1A1 • CTGF • ER • ERN1 • TGFB1

Business and Corporate Highlights (GlobeNewswire) - "Conducted a planned meeting with the FDA to discuss the design of a registrational study in DLB psychosis....'We are focused on initiating our Phase 3 study in mid-2027 with an improved tablet composition'....Extended the ongoing expanded access program for zervimesine in DLB through 2027 with funding from a second philanthropic donor."

Clinical • FDA event • New P3 trial • Dementia • Lewy Body Disease

Cognition Therapeutics Participating in Fireside Chat at B. Riley Securities' Mind, Muscle & Vision Summit (GlobeNewswire) - "During the discussion with analyst, William Wood, Ph.D., Ms. Ricciardi will review the status of the Company's ongoing START study as well as the planned initiation of a Phase 3 registrational study of zervimesine (CT1812) in dementia with Lewy bodies (DLB) psychosis."

New P3 trial • Trial status • Alzheimer's Disease • Dementia • Lewy Body Disease

Cognition Therapeutics Aligns on Key Aspects of Pivotal Study for Zervimesine (CT1812) in DLB Psychosis Following Receipt of FDA Meeting Minutes (GlobeNewswire) - "The FDA agreed that psychosis associated with dementia with Lewy bodies (DLB) could be an approvable outcome and reached alignment with the Company on key aspects of a pivotal trial to support a New Drug Application (NDA). The registrational program is expected to begin in mid-2027....As discussed with the FDA, Cognition expects the Phase 3 study will enroll people with DLB who experience psychosis symptoms of hallucinations and delusions. Patients receiving stable background treatment with off-label antipsychotic medications will be eligible. Following screening, participants will be randomized to receive either 100 mg of once-daily oral zervimesine or placebo for nine months. The company will work with the FDA on the analytical and statistical details for the use of the neuropsychiatric inventory (NPI) as a novel primary endpoint for a pivotal trial in DLB psychosis."

FDA event • New P3 trial • Dementia • Lewy Body Disease

Cognition Therapeutics…announced that a Notice of Allowance has been received from the United States Patent and Trademark Office (USPTO) for patent application 19/563,468 (GlobeNewswire) - "The allowed patent covers a polymorphic crystalline form of zervimesine (CT1812), the company's lead drug candidate. Once issued, the patent will provide protection for this key formulation through 2045 and, if granted a standard 5-year extension, could offer protection through 2050....This patent application covers...methods of treating highly underserved, age-related degenerative disorders including Alzheimer’s disease, geographic atrophy, and dementia with Lewy bodies (DLB)."

Patent • Alzheimer's Disease • Dementia • Dry Age-related Macular Degeneration • Lewy Body Disease

Cognition Therapeutics Completes Meeting with FDA for Zervimesine (CT1812) in Dementia with Lewy Bodies with Psychosis (GlobeNewswire) - "The objective of this meeting was to review results from the Phase 2 study of zervimesine (CT1812) and discuss the design and endpoints of a registrational study in dementia with Lewy bodies (DLB) patients with psychosis....'The agency and we discussed the results from our Phase 2 COG1201 ‘SHIMMER’ Study in DLB and our proposed plan to advance zervimesine into a registrational program. We believe we have a path forward for the development of zervimesine for the treatment of DLB psychosis. We look forward to reviewing the FDA’s formal minutes in June.'"

FDA event • Dementia • Lewy Body Disease

Cognition Therapeutics Receives Second Philanthropic Donation to Extend Ongoing Expanded Access Program for Zervimesine (CT1812) in Dementia with Lewy Bodies (GlobeNewswire) - "The ongoing EAP has been extended to provide two years of treatment for participants....The open-label EAP (COG1202) was launched in 2025 with funding by a generous donation from the family of a DLB patient who was treated in the Phase 2 SHIMMER study. The EAP has since enrolled 32 individuals who are receiving 100 mg of once-daily oral zervimesine, a small molecule investigational therapy designed to protect synaptic function in patients with neurodegenerative diseases....The Company’s plans for the next trial(s) will be further informed by this meeting with the FDA and subsequent meeting minutes, both of which are expected in the second quarter of 2026."

FDA event • Financing • New trial • Dementia • Lewy Body Disease

Business and Corporate Highlights (GlobeNewswire) - "Requested a meeting with FDA Division of Psychiatry, which is expected to be conducted on May 20 with receipt of meeting minutes anticipated in June. Presented two posters at the AD/PD 2026 Alzheimer’s & Parkinson’s Diseases Conference: (i) an analysis of zervimesine’s effect on the components of the neuropsychiatric index, which was used in the Phase 2 COG1201 SHIMMER study (NCT05225415) in participants with DLB; and (ii) a proposed composite endpoint containing measures of memory, motor, fluctuations, behavior and psychosis, which may be an effective method of capturing the complexity of DLB symptoms in future clinical trials."

Clinical data • FDA event • P2 data • Dementia • Lewy Body Disease

Topline results from the 545-participant Phase 2 ‘START’ COG0203 (NCT05531656) study in mild cognitive impairment (MCI) and early Alzheimer's disease are anticipated in 2027 (GlobeNewswire)

P2 data • Alzheimer's Disease

Impact of zervimesine on the neuroinflammatory biomarker GFAP and related proteomic molecular correlates in plasma of participants from a phase 2 clinical trial in Alzheimer's disease. (PubMed, Alzheimers Res Ther) - No abstract available

Biomarker • Journal • P2 data • Alzheimer's Disease • CNS Disorders • Inflammation • GFAP

Randomized, double-blind study of zervimesine in mild to moderate Alzheimer's disease. (PubMed, J Alzheimers Dis) - P2 | "More robust treatment differences were observed in the below median baseline plasma p-tau217 group suggesting potentially greater efficacy of zervimesine in less advanced AD. These results support larger pivotal trials with zervimesine.Registered at clinicaltrials.gov: NCT03507790."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Aβ42

Cognition Therapeutics CEO Issues Letter to Shareholders (GlobeNewswire) - "In the second quarter of 2026, we expect to meet with the FDA’s Division of Psychiatry to discuss next steps in our registrational plan for DLB psychosis...The fully enrolled START study is our Phase 2 study in 545 participants with MCI and early Alzheimer’s disease...As a reminder, the START trial has been fully funded by an NIH grant and costs are covered through the completion of the study in 2027. Once we see the final results from this trial in the second half of 2027, we will assess next steps for the treatment of Alzheimer’s disease."

FDA event • P2 data • Trial completion date • Alzheimer's Disease • Dementia • Lewy Body Disease

Clinical and Operational Highlights:…Alzheimer’s disease (GlobeNewswire) - "Completed enrollment in December 2025 in Phase 2 ‘START’ COG0203 (NCT05531656) study in mild cognitive impairment (MCI) and early Alzheimer's disease; topline results expected in 2027."

Enrollment closed • P2 data • Alzheimer's Disease

A GLOBAL STATISTICAL TEST APPROACH TO CLINICAL TRIALS WITH ZERVIMESINE FOR DEMENTIA WITH LEWY BODIES (ADPD 2026) - "The proposed GST composite approach allows assessment of a general treatment effect in DLB without specifying a single-symptom primary outcome in patients displaying a multitude of symptoms. Future discussions with regulators may establish the acceptability of the GST approach for regulatory approval in DLB."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Mood Disorders • Movement Disorders

ZERVIMESINE SLOWS PROGRESSION OF SYMPTOMS IN MILD TO MODERATE DLB (ADPD 2026) - P2 | "Zervimesine was generally safe and tolerable with trends for slowing progression across all symptom domains with notable benefits observed for neuropsychiatric symptoms, memory related items and activities of daily living. Cognition Therapeutics will be meeting with FDA to discuss zervimesine DLB development plans."

Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Mood Disorders • Movement Disorders

Cognition Therapeutics Advancing Zervimesine (CT1812) for Dementia with Lewy Bodies (DLB) Psychosis (Yahoo Finance) - "As planned, the next study for DLB will focus on the measurement of neuropsychiatric symptoms such as hallucinations and delusions, and behavioral symptoms such as anxiety, aggression, and agitation...Participants will be randomized to either 100mg of oral zervimesine or placebo daily for the study period, after which participants would be eligible to enroll in an open-label extension study. Cognition expects to meet with the FDA Division of Psychiatry to discuss a DLB psychosis program by midyear 2026."

New trial • Dementia • Lewy Body Disease

Cognition Therapeutics Extends Expanded Access Program for Zervimesine (CT1812) in Dementia with Lewy Bodies (GlobeNewswire) - "The program, which was originally expected to provide each participant with twelve months of treatment, will now allow several more months of treatment....Thirty-two individuals were enrolled at eight sites in this open-label EAP, each of whom are being treated with 100 mg of oral zervimesine daily. Banner Sun Health Research Institute in Arizona was the first site to be activated and enrolled the first participants....The EAP is part of the company’s larger clinical development program in DLB, which included the Phase 2 SHIMMER study and planned clinical programs."

Clinical • Dementia • Lewy Body Disease

Cognition Therapeutics Completes Type C Meeting with FDA for Zervimesine (CT1812) in Dementia with Lewy Bodies (GlobeNewswire) - "The objective of this meeting was to review plans for the proposed Phase 2b study of zervimesine in dementia with Lewy bodies (DLB), a disease with no FDA-approved therapies."

FDA event • New P2b trial • Dementia • Lewy Body Disease

Biomarkers. (PubMed, Alzheimers Dement) - P2 | "The correlates identified may represent an inflammatory signature tied to the decreased neuroinflammation (plasma-GFAP) with zervimesine in AD patients observed in the pTau217 biomarker-defined subgroup (below the median). Results support a role for zervimesine in decreasing neuroinflammation and the continued clinical development of zervimesine for AD."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Inflammation • GFAP • LAMP1

Drug Development. (PubMed, Alzheimers Dement) - "Results from the SHINE study provide compelling evidence that zervimesine has the potential to slow cognitive decline in patients with AD. Participants with lower disease burden, as measured by plasma p-tau217 experienced a more pronounced treatment effect. Importantly, this benefit was observed in people across the mild-to-moderate MMSE spectrum. While preliminary, these results suggest that having a lower disease burden as measured by plasma p-tau217 may provide a therapeutic window to still treat patients in the moderate MMSE range. SHINE was supported by a grant from the National Institute of Aging (R01AG058660)."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease

Drug Development. (PubMed, Alzheimers Dement) - P2 | "In a pre-specified subgroup exhibiting 95% slowing of cognitive impairment with zervimesine, we identified protein correlates of cognition related to amyloid biology, supporting zervimesine mechanism of action. Enriching the mITT analysis with correlates from this biomarker-defined patient population reinforced observations of immune response and synaptic pathways that correlate with cognition in both mITT and below-median pTau217 subgroup. These biomarker findings paired with positive clinical outcomes support the further clinical development of zervimesine for AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Drug Development. (PubMed, Alzheimers Dement) - "These data will allow comparison of the SHIMMER population to prior DLB study populations. SHIMMER results support the potential for zervimesine to slow clinical progression in patients with mild-to-moderate DLB. The robust therapeutic response observed across neuropsychiatric, cognitive, motor and functional measures is particularly encouraging. An analysis of participant characteristics will help guide recruitment in future clinical studies of zervimesine and its potential use to treat people with DLB. Cognition Therapeutics conducted COG1201 with University of Miami Miller School of Medicine and the Lewy Body Dementia Association under a grant from the National Institute of Aging (R01AG071643)."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry

Phase 2 study of zervimesine (CT1812) in participants with mild-to-moderate dementia with Lewy bodies (DLB). (PubMed, Alzheimers Dement) - P2 | "This study evaluated the safety and efficacy of zervimesine in Lewy body dementia. The incidence of adverse events was comparable to zervimesine 100 mg and placebo. Favorable, consistent trends were observed with zervimesine for exploratory endpoints."

Clinical • Journal • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease