Slide 1: SEQUEL (COG0202) Topline Results
SEQUEL (COG0202) Topline Results A Pilot Electroencephalography (EEG) Study to Evaluate the Effect of CT1812 Treatment on Synaptic Activity in Subjects with Mild to Moderate Alzheimer’s Disease
Slide 2: Forward-Looking Statements
2 FORWARD-LOOKING STATEMENTS This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this presentation, other than statements of historical facts or statements that relate to present facts or curren
Slide 3: SEQUEL Hypothesis
3 • Aβ oligomers impair synaptic and neuronal activity • Will displacement of Aβ oligomers from synapses after treatment with CT1812 lead to a detectable change in EEG patterns? SEQUEL Hypothesis • Izzo NJ, et al. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer’s
Slide 4: SEQUEL: Single-site qEEG Study in Mild-to-moderate Alzheimer's Disease
4 Confidential SEQUEL (COG0202): Single-site qEEG Study in 16 Adults with Mild-to-moderate Alzheimer’s Disease Two-group cross-over design Inclusion Criteria Period One (4 weeks) Period Two (4 weeks) Assessments ‐ CSF positive for Aβ ‐ MRI consistent with Alzheimer's disease diagnosis ‐ MMSE 18-26 ‐
Slide 5: Design: Two-group cross-over study in mild-to-moderate AD
5 Design: Two-group cross-over study in 16 adults with mild-to-moderate AD Single site: VUmc Alzheimer’s Center, Amsterdam Primary objectives: • Assess safety, tolerability, PK of CT1812 following repeated dosing for 28 days • Evaluate efficacy of CT1812 in restoring synaptic function through quanti
Slide 6: Topline Data Overview
Topline Data Overview • Disposition and demographics • Safety and tolerability • Topline EEG findings
Slide 7: COG0202 Disposition and Demographics
7 • 34 subjects screened; 16 randomized • 15 completed the study - No subjects discontinued due to AEs - One patient discontinued after treatment period 1 due to withdrawal of consent (death in the family) • n=14 for placebo period (one participant missed visit 7); n=16 for CT1812 period • Mean Age:
Slide 8: SEQUEL: Safety and Tolerability
8 • CT1812 was well-tolerated - All AEs were mild and moderate - No Severe AEs, No SAEs, No AEs leading to death or discontinuation • TEAEs: - Occurred in 11 participants in the CT1812 period and 6 participants in the placebo period - 6 TEAEs were categorized as related to study drug (3 in CT1812 pe
Slide 9: Introducing quantitative EEG Biomarkers of Disease
9 • Amyloid burden can be measured by PET • Canonical biomarkers assessed via serum and blood • Anatomic changes can be measured by vMRI • Cognition and executive function can be measured with ADAS-Cog and other scales • Neurophysiology / quantitative EEG: - Global and regional brain activity - Regi
Slide 10: Brain Waves – a Brief Primer
10 • An EEG reading compares electrical activity between electrodes on the scalp • Fast waves in the alpha and beta frequencies dominate healthy EEG patterns • Alzheimer's disease is associated with slower waves – a theta or delta pattern • The dominance of one wave pattern over another is referred
Slide 11: SEQUEL: Topline EEG Data
11 Assess safety, tolerability, PK of CT1812 following repeated dosing for 28 days • Evaluate efficacy of CT1812 in restoring synaptic function through quantitative EEG as measured in rank order: - Global relative theta power (primary endpoint) - Global alpha AECC, global relative alpha power, globa
Slide 12: SEQUEL Topline Results
12 SEQUEL Topline Results Positive trends in first three ranked outcomes measures -0.0400 -0.0300 -0.0200 -0.0100 0.0000 0.0100 0.0200 0.0300 Global Relative Theta Power CT1812 Placebo normalizing p=0.123 * Nominally significant -0.02 -0.015 -0.01 -0.005 0 0.005 0.01 0.015 Global Alpha AECc (Connect
Slide 13: SEQUEL Topline Results: Global Relative Theta Power
13 • CT1812 treatment was associated with a reduction in global relative theta power Positive trends in brain activity - reduced global & regional theta power - following 4 wks of treatment SEQUEL Topline Results -0.0300 -0.0200 -0.0100 0.0000 0.0100 0.0200 0.0300 Global Relative Theta Power CT1812
Slide 14: SEQUEL Topline Results: Regional Relative Theta Power
14 • Decreases in relative theta power were also observed in specific brain regions: frontal, temporal, posterior (parietal and occipital), and central - Statistical significance was only achieved in the central region (p<0.006) Positive trends in brain activity - reduced regional theta power - f
Slide 15: SEQUEL Topline Results: Increased Connectivity
15 • In addition, an analysis of the qEEG results showed that CT1812 treatment was associated with greater connectivity between brain regions - This suggests that the brain’s ability to communicate and exchange information between regions can be rescued by CT1812 Positive trends in brain activity -
Slide 16: SEQUEL Topline Results: Increased Alpha Power
16 • Increases in relative power in the alpha band were observed globally - Fast alpha waves are considered to be part of the normal background rhythm of a healthy brain - In Alzheimer’s, alpha waves lose their dominance and are gradually replaced by slower-oscillating, lower-amplitude theta and d
Slide 17: Conclusions
17 • CT1812 was well tolerated in this 28-day study - All AEs were mild to moderate - There were no serious or severe AEs - No AEs led to study discontinuation or death • Strong trends on pre-specified qEEG measures - Consistent trend across all qEEG measures - Nominally significant treatment diffe
Slide 18: Evidence of CT1812 Impact on Alzheimer's Disease
18 • Studies to date provide evidence of: - Target engagement (SNAP) - Anatomical effect (SPARC) - Preliminary cognitive improvement (SHINE cohort A) - Neurophysiology (SEQUEL) • Supportive biomarker evidence of biological effect • Fully funded proof-of-concept studies ongoing: - Early Alzheimer’s d
Slide 19: Multiple Near-term Catalysts Expected
19 Alzheimer's Development DLB Development GA / Dry AMD Development 2019 2020 2021 2022 2023 2024 2025 Ph2 SHINE (COG0201) Mild-Mod AD Ph2 START (COG0203) Early AD Ph2 SEQUEL (COG0202) qEEG Ph2 SHIMMER (COG1201) DLB Ph2 MAGNIFY (COG2201) GA Topline SHINE Topline End-of-Phase 2 meeting SHIMMER Toplin
Slide 20: Thank You
Thank You Tony Caggiano, MD, PhD CMO and Head of R&D 914-221-6730 acaggiano@cogrx.com Lisa Ricciardi President & CEO 917-658-5789 lricciardi@cogrx.com John Doyle Chief Financial Officer 603-860-1078 jdoyle@cogrx.com