Cognition Therapeutics Targets Faster DLB Psychosis Path as Zervimesine Nears Late-Stage Plans

Key Points

• Zervimesine (CT1812) is being advanced toward late‑stage development with an initial, faster registrational focus on psychosis in dementia with Lewy bodies (DLB) after SHIMMER showed the strongest effects on hallucinations and delusions; Cognition will consult the FDA’s Division of Psychiatry and expects to begin DLB enrollment in Q1 2027.
• Cognition is planning Phase III Alzheimer’s trials using biomarker enrichment for low plasma p‑tau217 after SHINE indicated much stronger benefit in that subgroup (38% slower ADAS‑Cog decline overall and near‑complete slowing in the low p‑tau217 subset), while the larger START trial (545 patients) is ongoing with results expected in mid‑2027.
• The company intends to use a 100 mg dose for pivotal studies, reports a favorable safety profile (mainly mild, reversible AST/ALT elevations with >450 patients treated), and has about $37M in cash plus ~$36M in remaining grant funding, projecting runway into June 2027.

Cognition Therapeutics NASDAQ: CGTX executives told investors at the Needham conference that the company is preparing to advance its once-daily oral candidate zervimesine into late-stage development, with an initial focus on psychosis symptoms in dementia with Lewy bodies (DLB) while continuing to run a large National Institute on Aging (NIA)-funded Alzheimer’s disease study.

Pipeline focus shifts to DLB psychosis for a faster path

CEO Lisa Ricciardi said the company’s next planned study is in DLB psychosis, citing both prior clinical results and the burden psychosis places on families and care systems. Ricciardi argued that when patients develop psychosis, they often can no longer be cared for at home, leading to institutionalization and higher costs.

Chief Medical Officer Anthony Caggiano said the company recently met with the U.S. Food and Drug Administration (FDA) to discuss a registrational strategy in DLB. He said both Cognition and the FDA agreed the “strongest signal” in the company’s SHIMMER study was in hallucinations and delusions, prompting the plan to consult the FDA’s Division of Psychiatry for guidance on trials aimed at those symptoms. Caggiano said that meeting is expected later this year, with an update to follow.

In Q&A, Caggiano said the emphasis on psychosis is driven by practicality and the strength of the data: a trial focused on hallucinations and delusions could be “much smaller, much faster, and therefore cheaper and faster to market.” He added that while broader symptom improvements remain of interest, “there isn’t a good way to just look globally at function for people that have dementia with Lewy bodies,” making a focused indication the clearest path.

SHIMMER data highlighted neuropsychiatric and caregiver distress measures

Caggiano reviewed results from SHIMMER (COG1201), a six-month, 130-patient DLB trial supported by a $30 million NIA grant. Participants were randomized to two doses of zervimesine (also referred to as CT1812 in the presentation) or placebo. Because it was the company’s first DLB study, Cognition evaluated multiple symptom domains, including neuropsychiatric symptoms, cognition, symptom fluctuations, motor function, and activities of daily living.

He described what he called a consistent effect across symptom domains, presenting results as a percentage slowing of worsening versus placebo. He singled out neuropsychiatric symptoms—particularly hallucinations and delusions—as among the most notable effects.

Caggiano also emphasized caregiver impact, describing results from the Neuropsychiatric Inventory (NPI) Distress Scale. He said caregiver distress worsened over time in the placebo group but remained near baseline in the treatment groups, with distress improvements aligned with the same symptom categories clinicians observed, including anxiety, delusions, hallucinations, agitation, and aggression.

Looking specifically at an NPI-4 subset (hallucinations, delusions, anxiety, and agitation), Caggiano said the treatment effect was strong, citing a p-value of 0.001 comparing progression on placebo versus drug.

The company is also running an expanded access program in DLB, providing 100 mg daily dosing. Caggiano said the program was initially designed for 12 months and has since been expected to extend for many participants. Ricciardi noted the company receives “anecdotal feedback” from families that patients are doing better, while cautioning that such observations are not scientific evidence.

Alzheimer’s strategy: Phase III planning and biomarker enrichment

Caggiano said Cognition also held an end-of-phase II meeting with the FDA for Alzheimer’s disease to align on phase III design. He said the company and FDA agreed on trials in mild to moderate Alzheimer’s disease that would enrich for patients with baseline plasma p-tau217 below a specified threshold. The planned trials would be six months long, compare a single 100 mg dose to placebo, and use traditional endpoints such as ADAS-Cog and ADCS-ADL. He added that FDA agreed Cognition could also use composite outcome measures similar to those used in the Lilly and Eisai antibody trials, and that the program would likely include an open-label extension.

Discussing SHINE, a six-month, 150-patient mild-to-moderate Alzheimer’s trial conducted across multiple countries, Caggiano said Cognition analyzed outcomes in participants with lower baseline p-tau217, describing that approach as informed by published findings from the donanemab and lecanemab programs. In SHINE, he said patients treated with zervimesine worsened 38% slower on ADAS-Cog 11 versus placebo in the broader analysis, and that in the lower p-tau217 subgroup the scores at study end were “very much the same as they were at the beginning of the study,” suggesting near-complete slowing on that scale. He also said the p-tau217 relationship appeared independent of whether a patient was clinically mild or more moderate at baseline.

START trial enrollment complete; concomitant antibody use allowed

Cognition’s largest ongoing study is START, an 18-month, 545-patient trial in mild cognitive impairment and early Alzheimer’s disease with amyloid confirmation by PET imaging. Caggiano said the primary endpoint is CDR Sum of Boxes, and the trial is being conducted with the Alzheimer’s Clinical Trials Consortium. Ricciardi said the study was supported by an NIA grant of roughly $81 million.

Ricciardi added that Cognition allowed patients taking background lecanemab or donanemab to enroll, estimating 15% to 20% of participants may be on concomitant therapy. She said that could provide insight on safety and potential efficacy signals for combination use.

Ricciardi clarified during Q&A that START did not enroll patients based on low p-tau217 because it began before the company had insights from SHINE, though she suggested many early-stage patients may have lower levels.

Dose selection, safety profile, and cash runway

For the planned pivotal DLB psychosis program, Caggiano said Cognition intends to move forward with the 100 mg dose. He said the clinical effects at 100 mg and 300 mg appeared “quite indistinguishable,” and that “less is safer,” with fewer adverse events.

On safety, Caggiano said the drug has been well-tolerated across studies. He identified mild, reversible AST and ALT elevations as the main adverse event monitored, adding that these changes have not been associated with bilirubin increases or other indications of liver injury. Ricciardi said more than 450 patients have been treated with the drug to date and noted that in the company’s Alzheimer’s study there has been “no need for surveillance,” with “no ARIA anticipated” based on the mechanism.

Ricciardi also highlighted the company’s reliance on non-dilutive funding, stating Cognition has received about $170 million in grant income over time. She said the company reported $37 million in current cash, which she said is expected to fund operations into June 2027. She added the company has $36 million of remaining grant funding dedicated to completing the START trial.

Looking ahead, Ricciardi said the company expects to begin enrollment in a DLB study in the first quarter of 2027, while START is projected to complete last-patient visits by the end of the second quarter of 2027, with results anticipated in the second half of the third quarter of 2027.

About Cognition Therapeutics NASDAQ: CGTX

Cognition Therapeutics, Inc is a clinical-stage biopharmaceutical company focused on developing disease-modifying therapies for neurodegenerative disorders, with an emphasis on Alzheimer's disease. The company's lead investigational candidate, CT1812, is an oral small molecule that antagonizes the sigma-2 receptor complex to protect synapses from amyloid-beta oligomer toxicity. By targeting a novel mechanism of action, Cognition Therapeutics aims to slow or reverse cognitive decline in patients living with Alzheimer's disease.

CT1812 has successfully completed Phase 1 safety studies and preliminary Phase 2a trials, and is currently being evaluated in multiple Phase 2 clinical studies across North America and Europe in patients with mild-to-moderate Alzheimer's disease.

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