EX-99.2 3 tm2319819d2_ex99-2.htm EXHIBIT 99.2
Exhibit 99.2

| 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

| 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 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, are forward-looking statements. 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| 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 disease modification. Alzheimer’s Dement. 2021;1–18 • Izzo NJ, et al. Alzheimer’s therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity PLoS One. 2014 Nov 12; 9(11):e111899 • Izzo NJ, et al. Alzheimer’s therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits PLoS One. 2014 Nov 12; 9(11):e111898 • Limegrover, CS, et al. Alzheimer’s Protection Effect of A673T Mutation May Be Driven by Lower Aβ Oligomer Binding Affinity. J Neurochem. 2020; 00: 1– 15. doi:10.1111/jnc.15212 CT1812 Small Molecule TMEM97 PGRMC1 LilrB2 NoGo PrPc

| 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 ‐ No add’l CNS disorders ‐ Safety and PK ‐ Measurement of synaptic function via qEEG by relative theta power ‐ CSF and plasma biomarkers ‐ Cognition (ADAS-Cog-14, ADCS-CGIC, A-IADL-Q, NTB)* 1:1 Oral QD Administration Placebo (n=8) CT1812 (n=8), 300mg CT1812, 300mg Placebo https://clinicaltrials.gov/ct2/show/NCT04735536

| 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 quantitative EEG as measured by: - Global relative theta power (primary endpoint) - Global alpha AECC, global relative alpha power, global relative beta power – key pre-specified exploratory endpoints - Additional pre-specified EEG exploratory endpoints Exploratory objectives: • Cognitive measures: impact of CT1812 on cognitive and global functioning, as measured by the following: - ADAS-Cog-14, ADCS-CGIC, A-IADL-Q - Neuropsychological test battery (NTB), Controlled Word Association Test (COWAT), Trail Making Test (TMT) Parts A & B, and Wechsler Memory Digit Span (VMDS) - Exploratory – biomarkers – pending Study Design

| Topline Data Overview • Disposition and demographics • Safety and tolerability • Topline EEG findings

| 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: 66.4 years • 50% Female • 100% White, non-Hispanic • Baseline cognitive measures: - Mean MMSE: 21.1 - ADAS-Cog14: 30.2 - Amsterdam IADL: 52.6 • ApoE genotypes: - 31.3% ApoE e3/e3 - 37.5% ApoE e3/e4 - 31.3% ApoE e4/e4 • Time since diagnosis: 1.14 years COG0202 Disposition and Demographics Disposition Demographics

| 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 period and 3 in placebo period) • Most common AEs by MedDRA system organ class: - GI: nausea, diarrhea - Injury & procedural complications: procedural headache • Consistent with previous studies – 1 participant with mild (2X ULN) elevated liver enzymes Safety and tolerability profile consistent with previous studies COG0202 SEQUEL: Safety and Tolerability

| 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 - Regional connectivity Introducing quantitative EEG Biomarkers of Disease

| 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 to as "relative power" Brain Waves – a Brief Primer

| 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, global relative beta power – key pre-specified exploratory endpoints - Additional pre-specified EEG exploratory endpoints SEQUEL: Topline EEG Data

| 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 (Connectivity) CT1812 Placebo normalizing * p=0.034 -0.0300 -0.0200 -0.0100 0.0000 0.0100 0.0200 0.0300 Global Relative Alpha Power CT1812 Placebo p=0.149 normalizing

| 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 Placebo p=0.123

| 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 - following 4 wks of treatment SEQUEL Topline Results -0.04 -0.03 -0.02 -0.01 0 0.01 0.02 0.03 Regional Relative Theta Power CT1812 Placebo Frontal Temporal Posterior Central p=0.168 p=0.253 p=0.300 p=0.006

| 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 - increased connectivity - observed following 4 wks of treatment SEQUEL Topline Results -0.015 -0.01 -0.005 0 0.005 0.01 0.015 0.02 Global Alpha AECc (Connectivity) CT1812 Placebo * p=0.034 * Nominally significant

| 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 delta waves ​ Positive trends in brain activity - increased alpha power - observed following 4 wks of treatment SEQUEL Topline Results -0.0300 -0.0200 -0.0100 0.0000 0.0100 0.0200 0.0300 Global Relative Alpha Power CT1812 Placebo p=0.149

| 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 differences including global alpha AECc and central relative theta power​ • In conclusion, CT1812 has demonstrated an impact on brain activity in mild-to-moderate Alzheimer’s patients Conclusions

| 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 disease - Mild-to-moderate Alzheimer’s disease - Dementia with Lewy bodies Evidence of CT1812 Impact on Alzheimer’s Disease

| 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 Topline End-of-Phase 2 meeting IND clearance Protocol clearance LPI FPI LPI LPI LPI SHINE/SPARC biomarker data Interim analysis (n=24) Multiple Near-term Catalysts Expected

| 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