Cognition Therapeutics, Inc. · NASDAQ:CGTX
Cognition Therapeutics — Investor Presentation (January 2022)
32 slides from Cognition Therapeutics's investor presentation, Jan 10, 2022
Slide 1: Disease-modifying medicines for degenerative disorders
Disease - modifying medicines for degenerative disorders January 2022
Slide 2: Forward-looking statements
2 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
Slide 3: Who We Are
3 Who We Are Targeting unmet needs in age - related degenerative disorders of the central nervous system and retina such as Alzheimer’s disease, dementia with Lewy bodies (DLB), dry age - related macular degeneration (dry AMD), and Parkinson’s disease Functionally distinct therapeutic approach focus
Slide 4: Addressing Degenerative Disease by Targeting Sigma-2
4 Addressing Degenerative Disease by Targeting Sigma - 2 ( σ - 2) σ - 2 receptor complex components, PGRMC1 and TMEM97, control or influence these processes Cellular Homeostasis Degeneration Dysfunction / Death Several key cellular processes (vesicle trafficking and autophagy) required for homeostas
Slide 5: Modulating σ-2 Receptor Restores Cellular Dysfunction
5 • CT1812 is orally available, penetrates the blood brain barrier and binds selectively to the σ - 2 receptor • The σ - 2 receptor complex is expressed in: - Brain : cortex, hippocampus, substantia nigra, cerebellum - Retina : retinal pigment epithelial (RPE) cells, retinal ganglion cells, photorec
Slide 6: Pipeline
6 Product Candidate Target Indication Preclinical Phase 1 Phase 2 Phase 3 Funding CT1812 SEQUEL Mild - moderate AD $3.3M CT1812 SHINE Mild - moderate AD $30M CT1812 ACTC Early - stage AD $81M CT1812 DLB $30M CT1812 Dry AMD * CT2168 Synucleinopathies † CT2074 Dry AMD Pipeline * Provided the FDA agree
Slide 7: Key Upcoming Milestones
7 Completing • PK • Human AME • SEQUEL Conducting • SHINE (cohort 2) • Phase 2 in DLB • Phase 2 with ACTC • Phase 2 in dry AMD * • IND - enabling studies for research compounds Key Upcoming Milestones * Subject to discussion with FDA 2021 2022 2023 Completed x SNAP x SPARC x SHINE (cohort 1) Complet
Slide 8: Lead Program: Review of CT1812 for Alzheimer's Disease
Review of CT1812 for the Treatment of Alzheimer’s Disease Cognition Lead Program:
Slide 9: Alzheimer's Disease Market Overview
9 • Approx. 6.2 million individuals in United States are afflicted with Alzheimer’s disease 1 - Approximately 35 million people worldwide 2 - Prevalence expected to double by 2050 1 • Direct healthcare costs for patients with Alzheimer’s and other dementias is estimated to exceed $300 billion in the
Slide 10: CT1812: A Synaptoprotective Approach to Alzheimer's Disease
10 • CT1812 penetrates the blood brain barrier and binds selectively to the σ - 2 receptor • By modulating σ - 2, CT1812 displaces and prevents oligomers from binding to neurons and clears them into CSF • Prevents synaptotoxicity and facilitates restoration of neuronal function CT1812: A Synaptoprot
Slide 11: Alzheimer's Clinical Program Overview
11 Alzheimer’s Clinical Program Overview Study SAD/MAD COG0101 (n=93) DDI COG0103 (n=15) COG0102 (n = 19) SNAP COG0104 (n=3) SPARC COG0105 (n = 23) SEQUEL COG0202 (n = 16) SHINE COG0201 (n = 120) ACTC COG0203 (n=540) Population Healthy Volunteers Mild - Moderate Alzheimer’s Mild - Moderate Alzheimer
Slide 12: Unique Protective Effect: A673T-APP Mutation Supports CT1812 MoA
12 • First variant associated with protection against Alzheimer’s disease 1 • Carriers are four times less likely to get Alzheimer’s disease than non - carriers 2 • Internal data demonstrates that mutant A β oligomers bind with four - fold lower affinity to neuronal synapses than normal protein • To
Slide 13: Evidence of Target Engagement: SNAP
13 Evidence of Target Engagement: SNAP (COG0104) First evidence of target engagement in humans, mirrors preclinical findings, corroborating our mechanism of action …and now in people with Alzheimer’s disease CT1812 oligomer receptor complex PGRMC1 σ - 2 receptor complex TMEM97 This displacement can
Slide 14: SHINE interim analysis
14 • 3 - point difference (ADAS - COG) between treated and untreated patients at day 185 • Clinically meaningful magnitude of change • Trend for improved cognitive outcomes Cognitive & Biological Outcomes • Statistically significantly lower A β protein (p=0.017) in treated vs placebo patients • Addi
Slide 15: SPARC Results
15 Study goals: 1. Primary objective: evaluate safety and tolerability of CT1812 2. Secondary objective: e valuate CT1812 via: o SV2A PET, FDG - PET, volumetric MRI and functional MRI o CSF biomarkers, cognitive and clinical endpoints Results: • Safety profile consistent with prior studies • Trend t
Slide 16: Safety and tolerability
16 • CT1812 is not approved for any indication. • No deaths or SAEs attributed to CT1812 have been reported in any studies (blinded or unblinded). • 96 of 150 subjects exposed to CT1812 experienced 239 TEAE’s, 66 reported as possibly related to study drug of which 9 were moderate or severe. • Notabl
Slide 17: Expanded Patient Population: Early AD
17 • COG0203: Phase 2 efficacy study, powered to show change in cognition: slowing or halting cognitive decline • Enrollment: 540 individuals with early Alzheimer’s disease • Initiate in 2022 • Conducted in collaboration with premier NIA - funded Alzheimer’s clinical trial group • Up to 35 leading
Slide 18: Synucleinopathies Cognition Pipeline
Synucleinopathies Disorders such as DLB and Parkinson’s disease that are characterized by deposits of α - synuclein aggregates (called Lewy bodies) that disrupt key cellular processes Cognition Pipeline:
Slide 19: Synucleinopathies are 2nd only to AD in Prevalence
19 • In the U.S., approximately 13 million people have a form of dementia 1 - DLB accounts for 1.4 million cases; and Parkinson’s disease 1 million cases; • Direct healthcare costs for patients with DLB are approximately $31.5 billion 2 ; approximately $25 billion 3 for Parkinson’s disease - For Par
Slide 20: σ-Modulators May be Disease Modifying in Synucleinopathies
20 σ - 2 Modulators May be Disease Modifying in Synucleinopathies Cellular and clinical biomarker evidence that σ - 2 modulators have a beneficial impact α SynO+Drug CTL Incubation with oligomers causes deficits in membrane trafficking rates ■ α - synO + drug Vehicle alone (no deficit) α - synuclein
Slide 21: DLB Phase 2 Funded with ~$30M NIA Grant
21 • Principal investigator: James E. Galvin, MD, MPH, professor of neurology and director of the Comprehensive Center for Brain Health • Initiate Phase 2* in 1H 2022 • U Miami and 20+ academic sites DLB Phase 2 Funded with ~$30M NIA Grant Placebo (N=40) CT1812 100 mg (N=40) Baseline 6 months CT1812
Slide 22: MJFF Grant Award Supports Further Study in Parkinson's Disease Models
22 • Jan 2022 cognition awarded a Therapeutic Pipeline Program Grant from The Michael J. Fox Foundation for Parkinson's Research (MJFF) • Will fund preclinical studies of two chemically distinct σ - 2 receptor modulators in animal models of Parkinson’s disease • Successful completion will inform sel
Slide 23: Dry Age-related Macular Degeneration Cognition Pipeline
Dry Age - related Macular Degeneration Cognition Pipeline:
Slide 24: Role of σ-2 Receptor Complex in Dry AMD
24 • Expression: In retinal pigment epithelial (RPE) cells, retinal ganglion cells, photoreceptors in retina • Human genetics: Linked to dry AMD • Biology : Regulates autophagy, protein trafficking, lipid metabolism dysregulated in dry AMD • Target validation: TMEM97 knockdown has been shown to be p
Slide 25: Human Genetics Points to a Role for TMEM97 in dAMD
25 Human Genetics Points to a Role for TMEM97 in dAMD GWAS identified a SNP in TMEM97 - VTN locus that confers decreased risk of dAMD Locus identified in several independent and large - scale GWAS Yan et al. Human Molecular Genetics, 2018
Slide 26: Rationale for σ-2 Modulators in Dry AMD
26 • Clinical support: Proteomics analyses showed differential movement of proteins involved in dry AMD • Preclinical data: Regulates inflammatory response, ameliorate trafficking deficits and prevents cell death Goal: protect RPE cells from disease - relevant stressors Rationale for σ - 2 Modulator
Slide 27: Pathway Analysis of Patient Proteomics Data Implicates CT1812 in dAMD
27 Unbiased Pathway Analysis of Patient Clinical Trial Proteomics Data Implicates CT1812 in dAMD 1. Generated list of proteins differentially expressed in CSF from CT1812 - vs. placebo - treated patients for each trial*timepoint 2. Performed Metacore pathway analysis of CSF (CT1812 vs placebo) acros
Slide 28: Analysis of Alzheimer's Patient Clinical Trial Data
28 Proteins Altered by CT1812 vs placebo in AD patient biofluids (SHINE - A clinical trial) Proteins Dysregulated in dry AMD tissue and biofluids ( dAMD vs control) PPI enrichment p - value: 9.2e - 09 STRING Protein Interaction Network V11.0 B String Oct 2020 release. Enabled the identification of a
Slide 29: σ-Modulators Rescue RPE Deficits and May be Protective in Dry AMD
29 Data Indicate σ - 2 Modulators Rescue RPE Deficits and May be Protective in Dry AMD Cell Survival and Inflammatory Pathways are Altered by CT1812 vs Vehicle (p<0.05) u n t r e a t e d t r i g g e r + c o n t r o l 3 n M 3 0 n M 3 0 0 n M 3 u M 3 n M 3 0 n M 3 0 0 n M 3 u M 0 25 50 75 100 125 % Ce
Slide 30: Planned Phase 2 in dry AMD
30 Planned Phase 2* to enroll patients with diagnosed dry AMD and measurable GA Screening: • Age: ≥ 50 • Diagnosis of dry AMD • BCVA ≥ 24 letters (ETDRS) • GA lesion ≥ 2.5 and ≤17.5mm 2 Assessments: • Primary endpoints : - Change in GA lesion using fundus autofluorescence (FAF) • Secondary endpoints
Slide 31: Financial Position
Financial Position Capital Markets • IPO priced Oct 8 $45.2 million • Overallotment exercised Nov 15 $6.8 million - Total IPO proceeds (gross) $52.0 million NIA funding for CT1812 studies • Preclinical through Phase 2 studies $168.4 million • Approximate funding used ($58.0 million) - Available NIA
Slide 32: Thank You
Thank You James O’Brien Chief Financial Officer 203 - 536 - 1797 jobrien@cogrx.com Lisa Ricciardi President & CEO 917 - 658 - 5789 lricciardi@cogrx.com
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