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

Rhea-AI Summary

Cognition Therapeutics (NASDAQ: CGTX) reported new biomarker analysis from their Phase 2 'SHINE' study in mild-to-moderate Alzheimer's disease. The analysis revealed that patients with lower baseline plasma p-tau217 levels treated with CT1812 showed a 95% reduction in cognitive decline compared to placebo, representing a 2.7-point improvement on ADAS-Cog11 over six months. The study demonstrated normalization of key Alzheimer's disease indicators, including reductions in GFAP (neuroinflammatory biomarker), NfL (neurodegenerative biomarker), and impacts on amyloid biology through reductions in Aβ42 and Aβ40 proteins. The company plans to present complete biomarker results at scientific conferences in 2025.

Positive

• 95% reduction in cognitive decline in CT1812-treated patients with lower p-tau217 levels
• 2.7-point improvement on ADAS-Cog11 versus placebo over six months
• Demonstrated normalization of multiple key Alzheimer's disease biomarkers
• Evidence suggesting disease-modifying potential of CT1812

Negative

• Results to subset of patients with lower p-tau217 levels
• Phase 3 program design still pending FDA review

Insights

Medical Research Analyst

The biomarker analysis from Cognition Therapeutics' Phase 2 SHINE study reveals compelling evidence of CT1812's potential efficacy in treating Alzheimer's disease. The key findings show a remarkable 95% reduction in cognitive decline among patients with lower baseline p-tau217 levels, supported by improvements in multiple critical biomarkers.

The data demonstrates normalization of several key disease indicators: reduced GFAP (neuroinflammation), lowered NfL (neurodegeneration) and decreased Aβ42 and Aβ40 levels (amyloid pathology). The 2.7-point improvement in ADAS-Cog11 scores over six months is particularly significant, as even small improvements in this scale can indicate meaningful clinical benefits.

These results suggest CT1812 may have true disease-modifying potential, rather than just symptomatic relief. The correlation between cognitive benefits and biomarker improvements strengthens the validity of these findings and positions CT1812 as a promising candidate for Phase 3 trials.

Financial Analyst

For a micro-cap biotech with a market cap of $17.7M, these Phase 2 results could be transformative. The Alzheimer's drug market is projected to reach $5.7B by 2027 and CT1812's unique mechanism of action, coupled with impressive efficacy data, could position it for significant market penetration.

The upcoming FDA meeting to discuss Phase 3 trial design will be a important catalyst. Positive regulatory feedback could accelerate the development timeline and potentially attract partnership interest from larger pharmaceutical companies. However, investors should note that Phase 3 trials will require substantial funding, likely necessitating additional capital raises that could dilute existing shareholders.

- 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.

Forward-Looking Statements 
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding our product candidates, including CT1812, and any expected or implied benefits or results, including that initial clinical results observed with respect to CT1812 will be replicated in later trials, our clinical development plans, or the clinical meaning of any biomarker results, are forward-looking statements. These statements, including statements relating to the timing and expected results of our clinical trials and our regulatory plans involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: competition; our ability to secure new (and retain existing) grant funding; our ability to grow and manage growth, maintain relationships with suppliers and retain our management and key employees; our ability to successfully advance our current and future product candidates through development activities, preclinical studies and clinical trials and costs related thereto; uncertainties inherent in the results of preliminary data, pre-clinical studies and earlier-stage clinical trials being predictive of the results of early or later-stage clinical trials; the timing, scope and likelihood of regulatory filings and approvals, including regulatory approval of our product candidates; changes in applicable laws or regulations; the possibility that the we may be adversely affected by other economic, business or competitive factors, including ongoing economic uncertainty; our estimates of expenses and profitability; the evolution of the markets in which we compete; our ability to implement our strategic initiatives and continue to innovate our existing products; our ability to defend our intellectual property; impacts of ongoing global and regional conflicts on our business, supply chain and labor force; our ability to maintain the listing of our common stock on the Nasdaq Global Market and the risks and uncertainties described more fully in the “Risk Factors” section of our annual and quarterly reports filed with the Securities & Exchange Commission and are available at www.sec.gov. These risks are not exhaustive and we face both known and unknown risks. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. 

Contact Information:    Cognition Therapeutics, Inc.     info@cogrx.com

Casey McDonald (media)   Tiberend Strategic Advisors, Inc.      cmcdonald@tiberend.com

Mike Moyer (investors)  LifeSci Advisors  mmoyer@lifesciadvisors.com

FAQ

What were the key results of Cognition Therapeutics' (CGTX) SHINE study biomarker analysis?

The analysis showed a 95% reduction in cognitive decline in CT1812-treated patients with lower p-tau217 levels, along with improvements in key Alzheimer's disease biomarkers including GFAP, NfL, and amyloid proteins Aβ42 and Aβ40.

How much improvement did CT1812 show on the ADAS-Cog11 scale in the SHINE study?

CT1812-treated patients showed a 2.7-point improvement on the ADAS-Cog11 scale compared to placebo over the six-month study duration.

What biomarkers were normalized in CGTX's Phase 2 SHINE study?

The study showed normalization of GFAP (neuroinflammatory biomarker), NfL (neurodegenerative biomarker), and amyloid proteins Aβ42 and Aβ40 in patients treated with CT1812.