Cognition Therapeutics, Inc. · NASDAQ:CGTX
Cognition Therapeutics — Investor Day (April 2023)
44 slides from Cognition Therapeutics's investor day presentation, Apr 19, 2023
Slide 1: Developing disease-modifying medicines for degenerative disorders
Developing disease-modifying medicines for degenerative disorders Analyst Breakfast April 2023
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: Agenda
3 AGENDA 8:30 – 9:00 10:50 – 11:00 9:00 – 9:15 11:00 – 11:15 Arrivals / Breakfast 2023 – 2025 Outlook The CLINIC: A Review of our Ongoing and Planned Clinical Trials Welcome and Introductions The SCIENCE: Our Understanding of sigma-2 Receptor Biology Our RATIONALE CT1812 Biomarker Program Q&A Lisa R
Slide 4: Presenters for Today's Discussion
4 Presenters for Today's Discussion Lisa Ricciardi President & CEO Andrew Einhorn Interim CFO Anthony Caggiano, MD, Ph.D. CMO & Head of R&D Mary Hamby, Ph.D. VP, Research Paul Tiseo, Ph.D. VP, Clinical Development Britney Lizama, Ph.D. Research Scientist
Slide 5: Cognition Therapeutics Highlights
5 Protect synapses from toxic proteins and other stressors to facilitate restoration of neuronal function Cognition Therapeutics Highlights Novel Approach Validated Science CT1812 Oral Once-Daily Oligomer receptor: well characterized target Highly brain penetrant Selective and saturable binding Stro
Slide 6: Rigorous Phase 2 Programs Underway and Planned
6 Clinical Study Indication US Prevalence Grant Funding SEQUEL (n=23) Mild-moderate AD ~ 5 million $5.4 Million SHINE (n=144) Mild-moderate AD ~ 5 million $30 Million START (n=540) MCI & Early AD ~ 11 million $81 Million SHIMMER (n=120) Mild-moderate DLB ~1.4 million $30 Million MAGNIFY (n=240) GA s
Slide 7: Published in the International Journal of Molecular Sciences
7 Published in the International Journal of Molecular Sciences
Slide 8: Multiple Near-term Catalysts
8 2022 2023 2024 2025 Multiple Near-term Catalysts SHINE Phase 2 (Mild-mod Alzheimer’s / n=144) SHINE/SPARC biomarker SEQUEL (Mild-mod AD / qEEG) SHIMMER Phase 2 (Mild-mod DLB / n=120) GA IND Data readout Data readout Data readout Data readout START Phase 2 (Early Alzheimer’s / n=540) MAGNIFY Phase
Slide 9: The Science: Our Understanding of σ-2 Receptor Biology
Anthony Caggiano, MD, PhD CMO and Head of R&D The Science: Our Understanding of σ-2 Receptor Biology
Slide 10: Sigma-2 Modulation to Address Amyloid Toxicity
10 Aβ monomer Anti-oligomer Mab Sigma-2 Modulation to Address Amyloid Toxicity Anti-protofibril Mab Anti-plaque Mab Protect Synapses: • Small molecule ligand to the σ-2 receptor displaces Aβ oligomers and prevents their binding to synapses Lower Aβ: • Monoclonal antibodies bind to Aβ proteins • Immu
Slide 11: MoA and Rationale Based in Foundational Science
11 MoA and Rationale Based in Foundational Science
Slide 12: CT1812: The Molecule
CT1812: The Molecule al istry Letters) “Medic Discovery of Investigational Drug CT1812, an Antagonist of the Sigma-2 Receptor Complex for Alzheimer’s Disease Gilbert M. Rishton, Gary C. Look, Zhi-Jie Ni, Jason Zhang, Yingcai Wang, Yaodong Huang, Xiaodong Wu, Nicholas J. Izz0, Kelsie M LaBarbera, Col
Slide 13: CT1812 Displaces Oligomers
13 CT1812 Displaces Oligomers treatment prevention control A MAP2 Aβ42 oligomers B C in vitro displacement transgenic mice humans MIE Measurement Dose administration minutes % Basal CSF AβO CT1812 Placebo % 50 100 150 200 250 10000 20000 30000 300 MIE Measurement Dose administration hours % change A
Slide 14: Unique Protective Effect: A673T-APP Mutation Supports CT1812 MoA
14 • First variant associated with protection against Alzheimer’s disease1 – ‘Icelandic Mutation’ • Mutant Aβ oligomers bind with four-fold lower affinity to neuronal synapses than WT protein • Carriers are four times less likely to get Alzheimer’s disease than non-carriers2 • To our knowledge, CT18
Slide 15: Restores Synapses and Function
15 Restores Synapses and Function Trafficking in cultured neurons Morris water maze – Swim length
Slide 16: MOA Video
16 MOA Video Watch online: https://vimeo.com/800999561
Slide 17: CT1812 and σ-2 Biology
17 • Decade long publication history supporting the biology of σ-2 in neurodegenerative conditions • Robust basic science program defining the biological effects of σ-2 modulation and generating new molecules to address serious human disease • The lead molecule, CT1812, is in multiple proof of conce
Slide 18: CT1812 Biomarker Program
Britney Lizama, PhD Research Scientist CT1812 Biomarker Program
Slide 19: CT1812 Clinical Biomarker Posters
19 • AD/PD™ 2022 International Conference on Alzheimer’s and Parkinson’s Diseases; Barcelona, Spain. • 2022 Alzheimer’s Association’s International Conference (AAIC); San Diego, CA. CT1812 Clinical Biomarker Posters
Slide 20: Key Takeaways from 2022 Presentations
20 • Strong correlations of canonical AD biomarkers from clinically validated assays confirms proteomics method as a quantitative way of assessing the impact of CT1812 - SHINE-A and SPARC CSF AD biomarkers at baseline were similar to that of the AD group from an independent, well-characterized AD an
Slide 21: AD/PD 2023 International Conference on AD and PD
21 AD/PD™ 2023 International Conference on AD and PD Amyloid biology, synapse regulation Meta-analysis
Slide 22: σ-2 Receptor Special Issue
22 • Goal: summarize the evidence-based understanding of σ-2 receptor biology and function, and its potential as a therapeutic target for age-related CNS diseases • Diseases in focus - Alzheimer's disease - dementia with Lewy bodies - Dry age-related macular degeneration - Parkinson's disease • Key
Slide 23: Overview of the Clinical Program for CT1812
Paul J Tiseo, PhD VP & Head of Clinical Development Overview of the Clinical Program for CT1812
Slide 24: Overview of Clinical Study Program
24 Current PoC Studies • COG0201 – SHINE (6-month study in mild-to-moderate AD) • COG0202 – SEQUEL (quantitative EEG study in mild-to-moderate AD) • COG0203 – START (18-month study in early AD) • COG1201 – SHIMMER (6-month study in patients with dementia with Lewy bodies) Planned PoC Study • COG2201
Slide 25: SEQUEL (COG0202)
25 • Design: two-group cross-over design in patients with mild-to-moderate AD • Single site: VUmc Alzheimer’s Center (PI: E. Vijverberg, MD, PhD) • Objective: To evaluate changes in synaptic function through quantitative EEG, as reflected by cortical theta wave power • Last patient visit end of Apri
Slide 26: SEQUEL (COG0202): Single-site Study
26 SEQUEL (COG0202): Single-site Study Evaluating efficacy of CT1812 via quantitative EEG, as reflected by relative theta power LPLV: April 2023 with Topline Data: mid 2023 Screening Period One (4 weeks) Period Two (4 weeks) Assessments ‐ Labs ‐ Quantitative EEG ‐ MRI ‐ Brain amyloid via PET ‐ Quant
Slide 27: Nonclinical Testing Supports AβO Hypothesis for CT1812
27 Nonclinical Testing Supports AβO Hypothesis for CT1812 CT1812 Restores Cognitive Function in Mice CT1812 Vehicle Displaces Oligomers from AD Patient Brain Tissue CT1812 Displaces Oligomers in Mouse Model of AD Postmortem Alzheimer’s-confirmed brain tissue section (ThioS labeling) Izzo NJ et al. P
Slide 28: Evidence of Target Engagement: SNAP Study
28 Evidence of Target Engagement: SNAP Study First evidence of target engagement in humans, mirrors preclinical findings, corroborating our mechanism of action …and now in people with Alzheimer’s disease This displacement can be measured in the CSF in Alzheimer’s mice treated with CT1812 CT1812 mech
Slide 29: SHINE Phase 2 Study in Mild-to-moderate Alzheimer's Disease
29 Screening Treatment Period (6 mo) Assessments ‐ Diagnosis of Alzheimer’s disease ‐ MMSE 18-26 ‐ Labs ‐ MRI ‐ Brain amyloid via PET ‐ Cognitive testing ‐ Biomarkers (CSF/Plasma) Phase 2 Safety and Efficacy Study in Adults with Mild-to-moderate Alzheimer’s Disease Placebo (n=48) 1:1:1 CT1812 100 mg
Slide 30: Interim analysis yields promising results
30 • 3-point difference (ADAS-COG) observed between treated and untreated patients at day 185 • Clinically meaningful magnitude of change in 6 months • Trend for improved cognitive outcomes • Enrolling at sites in US and Europe Interim analysis yields promising results (n=24) Cognitive & Biological
Slide 31: Phase 2 Study in Dementia with Lewy Bodies
31 • Principal investigator: James E. Galvin, MD, MPH, professor of neurology and director of the Comprehensive Center for Brain Health • Funded by ~$30M NIA Grant • A total of 30 sites in the US • Study ongoing. N = 120 patients Phase 2 Study in Dementia with Lewy Bodies
Slide 32: Targeting Early Alzheimer's Disease: START
32 • A randomized, double-blind, placebo-controlled Phase 2 study in individuals with early-to-mild AD • Multi-site: 50-60 U.S. sites including ACTC centers of excellence • Objective: powered to show change in cognition; slowing or halting cognitive decline • Funding: $81M NIA grant award in collabo
Slide 33: New Indication: Geographic Atrophy Secondary to Dry AMD
Anthony Caggiano, MD, PhD CMO and Head of R&D New Indication: Geographic Atrophy Secondary to Dry Age-related Macular Degeneration
Slide 34: Rationale for σ-2 Modulators in Dry AMD
34 σ-2 receptors • Expression: in RPE cells, retinal ganglion cells, photoreceptors in retina • Biology: Regulates autophagy, protein trafficking, lipid metabolism dysregulated in AMD • Target validation: TMEM97 knockdown is protective • Human genetics: Linked to dry AMD σ-2 receptor modulators • No
Slide 35: Unbiased Pathway Analysis of Patient Proteomics Data Supports Targeting σ-2 for dAMD
35 Confidential Unbiased Pathway Analysis of Patient Clinical Trial Proteomics Data Supports Targeting σ-2 for dAMD 1. List of proteins differentially expressed in CSF from CT1812- vs. placebo-treated patients generated for each trial, timepoint 2. Metacore pathway analysis of CSF (CT1812 vs placebo
Slide 36: 2022 ARVO Annual Meeting
36 2022 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
Slide 37: σ-2 Receptor Modulators Rescue RPE Lysosomal Trafficking Deficits
37 σ-2 Receptor Modulators Rescue RPE Lysosomal Trafficking Deficits Receptor-bound POS Lysosome (LAMP 1/2) Autophagy Body (LC3b) Early Compartment (Rab 5) Rab 7 12 24 36 48 0.0 0.2 0.4 0.6 0.8 1.0 Time (hr) POS in LC3B+ autophagy bodies * * 12 24 36 48 0.0 0.2 0.4 0.6 0.8 1.0 Time (hr) POS in LC3B+
Slide 38: Dry AMD Endpoints: GA
38 • A fundus camera records images of the interior surface of the eye, providing visual detail of the retina, optic disc and macula • Fundus photography is used to determine the presence of drusen and GA lesions • In dry AMD, GA lesions are correlated with death of RPE cells and often precede notic
Slide 39: Dry AMD Clinical Development
39 • Genetic, biomarker and preclinical data demonstrate the potential of σ-2 modulation to improve outcomes in GA associated with dry AMD • GA is a large unmet medical need where recent successes have demonstrated a clear and objective path to regulatory approval • Coming soon: a phase 2 clinical t
Slide 40: Phase 2 Will Assess CT1812 in GA Secondary to Dry AMD
40 Phase 2 will Assess CT1812 in GA Secondary to Dry AMD Screening Treatment Period (24 mo) Assessments ‐ Age: ≥ 50 ‐ Diagnosis of dry AMD ‐ BCVA ≥ 24 letters (ETDRS) ‐ GA lesion ≥ 2.5 and ≤17.5mm2 ‐ Change in GA lesion area (FAF) ‐ Ellipsoid zone area (SD-OCT) ‐ Drusen volume (SD-OCT) 1:1 Placebo (
Slide 41: Finances and Conclusions
Andrew Einhorn Interim Chief Financial Officer Finances and Conclusions
Slide 42: Significant Grant Support from NIH
42 Grant funding for CT1812 studies as of Dec 31, 2022 • Cumulative grant awards: appx $171.0 million − Approximate funding used: ($81.7 million) − Remaining grant funding: $89.3 million Clinical Study Total Award NIA Grant Number START (early Alzheimer’s disease) $ 81 million AG065248 SHINE (mild-m
Slide 43: Financial Position
Financial Position Financials as of December 31, 2022 • Cash and Cash Equivalents: $41.6 million • Expected cash runway into the second half of 2024 Recent Financings • ATM initiated • Committed Equity Facility • Reverse inquiry November 2022
Slide 44: 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 Andy Einhorn Chief Financial Officer 973-879-8240 aeinhorn@cogrx.com