Cognition Therapeutics’ Analysis Correlates Biomarker Changes with Cognitive Benefit in Alzheimer’s Population

- Dramatic 95% Reduction of Cognitive Decline in CT1812-treated Patients with Lower Plasma p-tau217 Correlated with Improvements in Key Indicators of Alzheimer’s Disease Biology -

- Findings Support Disease-modifying Potential of CT1812 -

PURCHASE, N.Y., Nov. 25, 2024 (GLOBE NEWSWIRE) -- Cognition Therapeutics, Inc., (NASDAQ: CGTX), a clinical-stage company developing drugs to treat neurodegenerative disorders, provided an update on a biomarker¹ analysis from the Phase 2 ‘SHINE’ study in mild-to-moderate Alzheimer’s disease. This new analysis focused on plasma samples from all participants who entered the study with lower levels of plasma p-tau217². Several blood-based measures of Alzheimer’s disease biology were identified that were normalized in CT1812-treated participants compared to the placebo-treated participants. These biomarker changes occurred in concert with a 95% slowing of cognitive decline as measured by ADAS-Cog11 in the same patients. These data provide further evidence that CT1812 may be preserving cognitive function and slowing disease progression by protecting key neurological system.

A pre-specified analysis of SHINE participants defined by their baseline plasma p-tau217 concentrations was presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference in October 2024. SHINE participants treated with CT1812 who entered the study with lower plasma p-tau217 experienced a 95% slowing of cognitive decline as measured by ADAS-Cog11 when compared with placebo. This robust clinical benefit represented a 2.7-point improvement on ADAS-Cog11 versus placebo over the six-month study duration.

In this new analysis, the Company reported changes in plasma biomarkers that may reflect Alzheimer's disease pathology. The results demonstrated that individuals who entered the study with plasma p-tau217 below the median experienced a normalization of several key indicators of Alzheimer’s disease progression, including:

• Reduction in the neuroinflammatory biomarker, GFAP, an emerging biomarker of brain injury
• Lowering of the neurodegenerative biomarker, NfL, an indicator of the degree of neurodegeneration
• Impact on amyloid biology demonstrated by a reduction in Aβ42 and Aβ40, key proteins implicated in Alzheimer’s disease
  
  

“We now have evidence that the dramatic reduction of cognitive decline that was sustained over 6 months in patients treated with CT1812 who had lower plasma p-tau217 levels also was associated with improvements in key indicators of brain cell function. This finding gives us confidence that CT1812 is having a disease-modifying effect,” explained Anthony O. Caggiano, MD, PhD, Cognition’s CMO and head of R&D. “We expect to make a full presentation of these and other biomarker results at scientific conferences in 2025. In addition, we look forward to meeting with the FDA to review these compelling clinical and biomarker findings and aligning on a Phase 3 program design.”

1)  In this context, a biomarker is a protein that is involved in a normal or abnormal biological process that can be measured to determine if that biological process is being improved or worsened by drug intervention.
2)  See description of p-tau217 in the SHINE study below.

Abbreviations: ADAS-Cog11: Alzheimer's Disease Assessment Scale-Cognitive Subscale (11-task version); GFAP: glial fibrillary acidic protein; NfL: neurofilament light chain; Aβ: amyloid beta

About the SHINE Study
The COG0201 ‘SHINE’ study was a double-blind, placebo-controlled Phase 2 study that enrolled 153 adults with mild-to-moderate Alzheimer’s disease. The primary endpoint was safety and tolerability. Changes in cognition (ADAS-Cog 11, cognitive composite and MMSE) and function (ADCS-ADL and ADCS-CGIC) were also measured. Participants were evenly randomized to receive either placebo or one of two doses of CT1812 (100 mg or 300 mg), which was taken orally daily for six months. The SHINE study was supported by two grant awards from the National Institute on Aging of the National Institutes of Health (NIH) totaling approximately $30 million. More information may be found at clinicaltrials.gov under trial ID NCT03507790.

About p-Tau217 in the SHINE study
Tau is a protein that plays a number of important roles in neurons. When threonine 217, one of the amino acids in tau, is phosphorylated, the protein is referred to as “p-tau217.” P-tau217 is recognized as an important biomarker that has been shown to distinguish Alzheimer’s disease from other neurodegenerative disorders with a high degree of accuracy.

The SHINE study protocol called for an analysis of cognition and function scores based on plasma p-tau217 levels. All participants entering Cognition Therapeutics’ SHINE study were administered a blood test to measure levels of p-tau217 in their plasma. The median was calculated by taking the mid-point of all plasma p-tau217 levels for SHINE participants. In this study, the median baseline level of plasma p-tau217 was 1.0pg/mL. SHINE participants whose plasma p-tau217 levels were below 1.0pg/mL are referred to as having “lower” levels of plasma p-tau217. Likewise, SHINE participants with plasma p-tau217 concentrations above 1.0pg/mL are referred to as having “higher” levels.

Cognition believes p-tau217 will be an important and prominent biomarker in future CT1812 Alzheimer’s disease clinical trials.

About CT1812
CT1812 is an experimental orally delivered small molecule oligomer antagonist that penetrates the blood-brain barrier and binds selectively to the sigma-2 (σ-2) receptor complex. Preclinical and clinical data demonstrate that this binding results in the displacement of toxic Aβ oligomers. The σ-2 receptor complex is involved in the regulation of key cellular processes such as membrane trafficking and autophagy that are damaged by toxic interaction with Aβ oligomers, oxidative stress and other stressors. This damage to sensitive synapses can progress to a loss of synaptic function, which manifests as cognitive impairment and Alzheimer’s disease progression.

Participants are currently being recruited in the START study (NCT05531656) of CT1812 in adults with early Alzheimer’s disease; and the MAGNIFY study (NCT05893537) in adults with geographic atrophy (GA) secondary to dry age-related macular degeneration. Enrollment has completed in the SHIMMER study (NCT05225415) of CT1812 in adults with dementia with Lewy bodies and the aforementioned SHINE Study.

About Cognition Therapeutics, Inc. 
Cognition Therapeutics, Inc., is a clinical-stage biopharmaceutical company discovering and developing innovative, small molecule therapeutics targeting age-related degenerative disorders of the central nervous system and retina. We currently are investigating our lead candidate CT1812 in clinical programs in Alzheimer’s disease, dementia with Lewy bodies (DLB) and dry age-related macular degeneration (dry AMD). We believe CT1812 and our pipeline of σ-2 receptor modulators can regulate pathways that are impaired in these diseases that are functionally distinct from other approaches for the treatment of degenerative diseases. More about Cognition Therapeutics and our pipeline can be found at https://cogrx.com.

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