Cognition Therapeutics (NASDAQ:CGTX) Chief Executive Officer Lisa Ricciardi said at the Jefferies Global Healthcare Conference in New York that the company is preparing a registrational program for zervimesine, also known as CT1812, in Lewy body dementia psychosis.
Ricciardi described Cognition as a clinical-stage drug development company focused on central nervous system disorders, with lead programs in Lewy body dementia and Alzheimer’s disease. She said the company’s cash runway extends through June of next year and that grant funding of $25 million supports the company through the end of its clinical program.
Lewy Body Dementia Program Targets Psychosis
“Zero, right in the middle, that’s how many drugs are approved,” Ricciardi said, referring to therapies for hallucinations and delusions in the condition. She said psychosis is a leading reason patients with Lewy body dementia move out of their homes and into institutional care.
Ricciardi said current treatment relies on a “patchwork” of off-label medicines developed for other conditions, and that some existing neuropsychiatric drugs can be harmful for patients with Lewy body dementia. She said Cognition chose to focus on psychosis because the symptoms are prevalent, clinically significant and measurable using precedented endpoints.
Zervimesine Data From SHIMMER Trial
Cognition’s lead drug, zervimesine, is an oral small molecule that Ricciardi said the company expects to study at a 100 mg once-daily dose. She said the drug has shown a favorable safety profile in studies and that the company does not expect amyloid-related imaging abnormalities, or ARIA, based on its mechanism.
Ricciardi said the company’s Phase 2 SHIMMER trial enrolled 135 patients in the U.S. and evaluated two doses of zervimesine against placebo over six months. The study assessed multiple symptom categories in Lewy body dementia, including neuropsychiatric symptoms, cognition, movement, fluctuations, activities of daily living and clinician global assessment.
According to Ricciardi, placebo patients declined over six months, while patients receiving zervimesine showed better outcomes across the categories measured. She highlighted an 86% slowing of neuropsychiatric symptoms and an 89% slowing of hallucinations and delusions relative to placebo.
Ricciardi said the hallucinations and delusions data were central to discussions with the U.S. Food and Drug Administration. She said the agency suggested that focusing on those symptoms could produce the greatest impact.
Registrational Trial Planning Underway
Ricciardi said Cognition is now planning a registrational program in Lewy body dementia psychosis and has been working with the FDA’s psychiatry division. She said the company met with the agency about a week and a half before the conference and expects meeting minutes in several weeks.
The proposed study design under consideration includes one-to-one randomization of zervimesine 100 mg versus placebo, a possible nine-month treatment period and an endpoint based on the NPI-2 or a similar measure focused on hallucinations and delusions. Ricciardi said the company also expects to include an open-label extension to follow patients over time.
Key elements of the registrational plan remain undecided, including whether the trial will be domestic or international and whether one or two registrational studies will be required. Ricciardi said Cognition is also preparing to speak with European authorities.
Alzheimer’s Disease Program Continues
Ricciardi also discussed Cognition’s Alzheimer’s disease program. She said the company previously reported results from the Phase 2 SHINE trial, an international six-month study of 155 patients with mild-to-moderate Alzheimer’s disease that tested two doses of zervimesine.
In a prespecified analysis of patients with below-median phosphorylated tau, Ricciardi said zervimesine showed a 95% slowing of disease progression over six months. She said the company believes the six-month study may not have captured the full benefit of the drug.
Cognition is also conducting the START trial in early Alzheimer’s disease, including mild cognitive impairment and early-stage patients. Ricciardi said the 18-month trial was fully enrolled in December of last year and that the company expects the last patient to complete the trial around this time next year, with results to follow after data cleaning.
Ricciardi said the START trial allows for concomitant use with antibody therapies, reflecting the evolving standard of care after approvals of treatments such as Leqembi and Kisunla.
Funding and External Validation
Ricciardi said Cognition has received more than $170 million in grant funding from the National Institutes of Health and the National Institute on Aging. She also cited work with organizations including the Michael J. Fox Foundation and the Alzheimer’s Drug Discovery Foundation as external validation of the company’s science and clinical work.
She said patient demand has also been reflected in an expanded access program for zervimesine in Lewy body dementia, supported by families who wanted patients to remain on the drug after participating in the trial.
Ricciardi closed by describing Cognition as “data-driven” and focused on patient convenience through an oral drug approach, while continuing to work with regulators on established endpoints in a large unmet medical category.
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.
