Cognition Therapeutics (NASDAQ:CGTX) used its fourth-quarter and full-year 2025 earnings call to outline a shift in development priorities for its lead candidate, zervimesine (CT-1812), with management saying it will now focus on pursuing a registration path in dementia with Lewy bodies (DLB) psychosis.
Company prioritizes DLB psychosis after Phase II data and regulator feedback
Chief Executive Officer Lisa Ricciardi said the company has spent the past 18 months reporting Phase II results in DLB (the SHIMMER study) and mild to moderate Alzheimer’s disease (the SHINE study), and has also completed enrollment in the 18-month START trial in early Alzheimer’s disease. She added that the company has held meetings with U.S. and European regulators and, “with data in hand and feedback from regulators,” decided to prioritize zervimesine’s development for DLB psychosis.
Within behavioral symptoms, Caggiano said the effects were particularly notable for hallucinations and delusions—collectively referred to as psychosis. He said the company discussed the psychosis findings with the FDA during a Type C meeting in January and that the FDA agreed the effects on psychosis were compelling, directing Cognition to the FDA’s Division of Psychiatry to define a path toward registration.
Caggiano noted the Division of Psychiatry has overseen registrational studies and new drug applications for Rexulti (for Alzheimer’s agitation) and Nuplazid (for Parkinson’s disease psychosis). The company said a meeting request with the division has already been filed, and it expects to provide an update after receiving official meeting minutes “mid-year.”
Management emphasizes unmet need and potential for smaller registrational trials
On the call, Cognition emphasized both the prevalence and clinical burden of psychosis in DLB. Caggiano said psychosis is more prevalent in DLB than in other dementias and often occurs early, adding that as many as 80% of DLB patients experience psychosis and that hallucinations are among the core clinical criteria for a DLB diagnosis.
He also said there are no approved medications for DLB patients with psychosis and that many patients cannot tolerate traditional antipsychotics. While many development efforts in DLB psychosis focus on acute symptom treatment via receptor modulation, Cognition contrasted its approach, with Caggiano saying zervimesine is intended to interrupt basic disease pathophysiology and has shown robust efficacy over six months in certain DLB symptom domains, “most notably behavioral symptoms including psychosis.”
Caggiano added that in SHIMMER, patients with psychosis, anxiety, aggression, and agitation treated with zervimesine were stable compared with placebo participants whose symptoms worsened. Based on the strength of the psychosis signal, he said the company expects registrational studies focused on psychosis to be smaller and shorter than trials focused on cognition and general symptomatology, which management believes could expedite a path to market.
Expanded access program anecdotes reinforced the DLB focus
Ricciardi said anecdotal feedback from the company’s expanded access program (EAP) also supported the decision to pursue DLB psychosis. She said the EAP began in mid-2025 after a philanthropic donation from a patient’s family whose relative had been in the SHIMMER trial and wanted to maintain access to zervimesine.
According to Ricciardi, the EAP “quickly filled to capacity,” and the company continues to receive inquiries from patients and families seeking access or extended access. She noted the EAP is open-label, giving the company an opportunity to hear directly from patients and caregivers, and said the response has been consistent that participants believe zervimesine is making a tangible difference in daily life. Ricciardi said the company currently has funding to continue the EAP for another nine to 12 months.
Alzheimer’s development continues as START trial advances
While prioritizing DLB psychosis, Cognition said it remains committed to Alzheimer’s disease development. Ricciardi reviewed results from the Phase II SHINE study in mild to moderate Alzheimer’s disease, completed in 2024, in which the company reported a 38% reduction in cognitive decline versus placebo on the ADAS-Cog 11 scale. She said the magnitude was comparable to effects observed in Phase III trials for immunotherapies Kisunla and Leqembi, as described by management during the call.
Ricciardi added that in SHINE, the treatment effect was most pronounced in participants with lower blood levels of p-tau217, who experienced a 95% reduction in cognitive decline. She said that during a 2025 end-of-Phase II meeting, the FDA agreed with Cognition’s proposal to screen for participants with lower p-tau217 levels, which could expedite recruitment and enrich enrollment for those most likely to benefit.
The company also provided an update on START, its Phase II trial in mild cognitive impairment and early Alzheimer’s disease, stating it met its enrollment goal at the end of 2025 with 545 participants. Top-line results are expected in 2027 after the last participants complete the 18-month treatment period.
Financial results and 2026 operational updates
Chief Financial Officer John Doyle reported that cash, cash equivalents, and restricted cash equivalents totaled approximately $37 million as of December 31, 2025. He added that total grant funds remaining from the National Institute on Aging were $35.7 million, and the company estimates it has sufficient cash to fund operations and capital expenditures through the second quarter of 2027.
Doyle said research and development expenses were $37.2 million for the year ended December 31, 2025, down from $41.7 million in 2024, driven by completion of SHINE and SHIMMER and related professional fees. General and administrative expenses were $10.6 million, down from $12.3 million, primarily due to reduced stock-based compensation expense. Cognition reported a net loss of $23.5 million, or $0.32 per basic and diluted share, compared with a net loss of $34 million, or $0.86 per basic and diluted share, in 2024.
In the Q&A, management said its near-term priority is DLB and that it is not pursuing an ophthalmology program at this time. Executives also said additional supporting studies—including food-effect, drug-drug interaction, and other pharmacology work—are underway, along with a planned formulation change from a capsule to a tablet, with the company aiming to complete these activities during 2026.
When asked about combination use, management said prior studies were conducted on top of standard-of-care background medications, including acetylcholinesterase inhibitors and memantine in Alzheimer’s disease, and noted most DLB participants in SHIMMER were on acetylcholinesterase inhibitors. The company also said START allows participants to be on stable maintenance courses of immunotherapies such as lecanemab and donanemab, with an intent to collect information about potential additional benefit in combination.
In closing remarks, Ricciardi reiterated that Cognition is looking forward to meeting with the FDA’s Division of Psychiatry to finalize plans and timing for DLB psychosis studies, describing the indication as an important unmet need and pointing to both Phase II findings and feedback from the expanded access program.
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.
