Cognition Unveils Precision Phase 3 Plan for Oral Alzheimer's Drug

PURCHASE, NY – December 01, 2025 – Cognition Therapeutics, Inc. (NASDAQ: CGTX) has taken a significant step forward in the quest for a more effective and accessible Alzheimer's disease treatment, presenting a detailed Phase 3 clinical trial plan for its lead candidate, zervimesine (CT1812). Unveiled at the annual Clinical Trials on Alzheimer’s Disease (CTAD) conference, the strategy leverages a novel biomarker-driven approach that has already secured alignment from the U.S. Food and Drug Administration (FDA), potentially streamlining the path to market for the investigational oral drug.

The announcement signals a pivotal moment for the clinical-stage biopharmaceutical company, which aims to differentiate its once-daily pill in a field currently dominated by intravenously administered therapies. By targeting a specific patient sub-population, Cognition is embracing a precision medicine strategy that could enhance trial efficiency and, if successful, deliver a highly effective treatment to those most likely to benefit.

The Biomarker Breakthrough: A Precision Approach to Alzheimer's

Central to Cognition's strategy is the use of a blood-based biomarker, p-tau217, to enrich its trial population. The Phase 3 program will specifically enroll adults with mild-to-moderate Alzheimer's who exhibit lower levels of plasma p-tau217 at screening. This decision is not a speculative gambit but is directly informed by compelling data from the company's 153-patient Phase 2 SHINE study.

“Results from the Phase 2 ‘SHINE’ study showed that participants treated with zervimesine who had lower plasma p-tau217 levels experienced a 95% slowing of cognitive decline (by ADAS-Cog11) compared with placebo,” explained Anthony Caggiano, M.D., Ph.D., Cognition’s chief medical officer. “Seeing a robust therapeutic response in patients with lower p-tau levels was not surprising, given the experience reported from the approved monoclonal antibody treatments.”

The FDA's agreement with this enrichment strategy, confirmed during an End-of-Phase 2 meeting on July 9, 2025, represents a major regulatory validation. The use of p-tau217, a biomarker increasingly recognized for its accuracy in detecting Alzheimer's pathology—rivaling more invasive CSF analysis or costly PET scans—allows for a more targeted and efficient trial design. By screening patients with a simple blood test, Cognition can more easily identify and recruit individuals for whom the drug has already shown a profound effect, increasing the statistical power of the studies and potentially reducing overall costs and timelines. This approach stands as a significant innovation in a therapeutic area long plagued by high trial failure rates.

The Oral Advantage and a Novel Mechanism

Beyond its innovative trial design, zervimesine's profile as an oral, once-daily small molecule presents a substantial competitive advantage. The current standard-of-care treatments, such as amyloid-beta antibodies, require regular intravenous infusions in a clinical setting, creating logistical burdens for patients, caregivers, and healthcare systems. A safe and effective oral therapy would dramatically improve accessibility and patient quality of life. The Alzheimer's drug market, valued at over $7.7 billion in 2023, is projected to see oral therapies account for a majority share, highlighting a significant commercial opportunity for successful candidates like zervimesine.

Zervimesine also differentiates itself through a novel mechanism of action. It acts as a modulator of the sigma-2 receptor (S2R) complex, a target distinct from the direct amyloid plaque removal approach of antibody treatments. Zervimesine is designed to interfere with the toxic signaling of amyloid-beta (Aβ) oligomers at the synapse, effectively protecting neurons from damage, restoring synaptic function, and facilitating the clearance of these toxic proteins. This focus on synaptic protection, rather than just plaque clearance, offers a complementary and potentially synergistic therapeutic strategy in the fight against neurodegeneration.

While the market for oral Alzheimer's drugs is competitive, with candidates like Alzheon's ALZ-801 also in late-stage development, Cognition's dual advantage of a convenient oral formulation combined with a validated biomarker-targeting strategy positions it as a formidable contender. The company is betting that this precision approach will yield a cleaner efficacy signal and a stronger value proposition upon potential approval.

Navigating a Global Regulatory Gauntlet

The path forward for Cognition is becoming clearer and more streamlined. Following its productive meeting with the FDA, the company received meeting minutes on August 12, 2025, which outlined a surprisingly direct route to a potential New Drug Application (NDA). The FDA stated that two six-month Phase 3 studies, randomizing patients to a 100 mg dose of oral zervimesine or placebo, may be sufficient for a filing. This is a significant concession, as many late-stage neurology trials require 18 months or longer to demonstrate efficacy. These shorter studies, which will measure efficacy using the composite iADRS scale, will dramatically reduce the time and capital required to reach the next major regulatory milestone.

With a clear path in the U.S., Cognition is now turning its attention to Europe. “Cognition Therapeutics is planning to conduct a scientific advice meeting with the European Medicines Agency (EMA) to align global Alzheimer’s disease registrational plans with those discussed with FDA in July,” stated Lisa Ricciardi, president and CEO of Cognition. This meeting, scheduled for February 2026, is a critical step in executing a global development program and maximizing the drug's future market access.

Executing two global Phase 3 trials will nonetheless require substantial capital. While the company is burning through cash, a common feature of clinical-stage biotechs, its financial position is bolstered by significant non-dilutive funding. Cognition has secured approximately $111 million in grants from the National Institutes of Health (NIH) for its zervimesine programs, a powerful external validation of its science. This includes an $81 million grant for its ongoing START study in early Alzheimer's. This strong government backing, combined with a 332% surge in its stock price over the past year, reflects robust investor and scientific confidence. The company is now actively evaluating its resource allocation across its Alzheimer's and dementia with Lewy bodies (DLB) programs to ensure it can deliver on its ambitious clinical and regulatory timeline.