EX-99.1 2 tm2218577d1_ex99-1.htm EXHIBIT 99.1

Exhibit 99.1

Disease - modifying medicines for degenerative disorders JMP Securities Life Sciences Conference June 16, 2022

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 but not limited to, statements regarding the Company ’s cash and financial resources and its clinical development plans, are forward - looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results , p erformance, 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 statemen ts by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential ” o r “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 belie ve may affect our business, financial condition, and results of operations. These forward - looking statements speak only as of the date of this presentation and are subject to a number of risks, uncertainties and assumptions , s ome of which cannot be predicted or quantified and some of which are beyond our control, including, among others: our ability to successfully advance our current and future product candidates through development ac tiv ities, preclinical studies, and clinical trials; the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; the impact of the COVID - 19 pandemic on our busines s and operations; the performance of third parties in connection with the development of our product candidates, including third parties conducting our future clinical trials as well as third - party suppliers and manufactu rers; our ability to successfully commercialize our product candidates and develop sales and marketing capabilities, if our product candidates are approved; and our ability to maintain and successfully enforce adequate in tellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of our most recent filings with the Securities and Exchange Commission and are available at www.se c.g ov. 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 pos sib le 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. TRADEMARKS This presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the propert y o f their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this presentation may be listed without the TM, SM © or ® symbols, but the Company wil l assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and copyrights. MARKET & INDUSTRY DATA Projections, estimates, industry data and information contained in this presentation, including the size of and growth in key en d markets, are based on information from third - party sources and management estimates. Although the Company believes that its third party - sources are reliable, the Company cannot guarantee the accuracy or completene ss of its sources. The Company's management estimates are derived from third - party sources, publicly available information, the Company's knowledge of its industry and assumptions based on such information an d k nowledge. The Company's management estimates have not been verified by any independent source. All of the projections, estimates, market data and industry information used in this presentation involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such information. In addition, projections, estimates and assumptions relating to the Company's and its industry's future performa nce are necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including, but not limited to, those described above, that could cause future performance to differ materially from the Compa ny' s expressed projections, estimates and assumptions or those provided by third parties. Forward - looking Statement

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 focused on the sigma - 2 (σ - 2) receptor complex, backed by decades of expertise in the biology of synaptic function and plasticity Received over $160 million in non - dilutive funding through key collaborations with the National Institute of Aging and other thought - leading institutions − Approximately 50% of ongoing R&D expenses covered by grants Multiple Phase 2 programs expected to provide significant value - creating milestones and data readouts over the next 12 to 24 months Expanding pipeline through our proprietary NICE screening platform, strategic alliances and acquisitions Seasoned management team with broad scientific, drug development and commercial expertise; experienced board and advisors

4 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 START Early - stage AD $81M CT1812 SHIMMER DLB $30M CT1812 Dry AMD * CT2168 Synucleinopathies † CT2074 Dry AMD Pipeline * Provided the FDA agrees, we intend to proceed with a Phase 2 study supported by the Phase 1 AD studies † including Parkinson’s disease and DLB IND enabling studies IND enabling studies Please note: CT1812 and other pipeline candidates are not approved for use in the US or other jurisdictions

5 Clinical Study Total Awarded Remaining (yet to be drawn down) START (early AD) $ 81 Million $ 69 Million SHINE (mild/mod AD) $ 30 Million $ 13 Million SHIMMER (DLB) $ 29 Million $ 27 Million SEQUEL ( qEEG in AD) $ 3.3 Million $ 0.8 Million $ 144 Million $ 110 Million Approximately 50% of R&D Funded by Grants Grants Continue to Provide Funding NOTE: amounts are approximate dollar amounts as YE 2021

6 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) Completing • SHINE (cohort 2) Ongoing Studies • Phase 2 in DLB • Phase 2 with ACTC • Phase 2 in dry AMD Regulatory Actions • IND filings for pipeline compounds

Review of CT1812 for the Treatment of Alzheimer’s Disease Cognition Lead Program:

8 • 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 United States alone 1 - Projected to increase to $1+ trillion by 2050 1 Mild , 50.4% Moderate , 30.3% Severe , 19.3% Stages of Disease Afflicting Current Population of Alzheimer’s Patients Alzheimer’s Disease Market Overview 1) Economic Burden of Alzheimer Disease and Managed Care Considerations. Am J Manag Care. 2020;26:S177 - S183 2) World Health Organization Key Facts: Dementia

9 • CT1812 penetrates the blood - brain barrier (BBB) 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 mimics the protective effects of the A673T - APP “Icelandic” mutation CT1812: A Synaptoprotective Approach to Alzheimer’s Disease • Izzo NJ, et al. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer’s disease modification. A lzh eimer’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 A β Oligomer Binding Affinity. J Neurochem . 2020; 00: 1 – 15. doi:10.1111/jnc.15212 σ - 2 modulator Oligomer receptor Neuronal Synapse σ - 2 receptors A β oligomers

10 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 be measured in the CSF in Alzheimer’s mice treated with CT1812 CT1812 mechanism of action: By binding to the σ - 2 receptor, CT1812 displaces A β oligomers from synapses, thus preventing synaptic toxicity MIE Measurement – CT1812 Dose administration hours % change ABOs in CSF v baseline MIE Measurement - Placebo hours Dose administration % change ABOs in CSF v baseline minutes MIE Measurement – Vehicle Dose administration % Basal CSF A β O MIE Measurement – CT1812 Dose administration minutes % Basal CSF A β O Izzo, NJ et al. Alzheimer's Dement. 2021; 17: 1365 - 1382. https://doi.org/10.1002/alz.12302 SNAP COG0104 study (NCT03522129) funded by NIA grant 1RF1AG057780

11 • 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 • Additional analyses on p - tau, synaptic and AD - related proteins ongoing Placebo CT1812 100 mg Day 0 6 months 1:1:1 Study Design (n=120) Screening: Labs, exams, MRI, brain amyloid PET Assessments: Cognitive testing, Biomarkers (CSF/Plasma) CT1812 300 mg SHINE interim analysis (n=24) yields promising evidence All doses: QD, oral SHINE COG0201 study (NCT03507790) funded by NIA grant R01AG058660

12 1 ° Endpoint: evaluate safety and tolerability of CT1812 Results: • Safety profile consistent with prior studies • Trend towards preservation of brain volume (composite) in treated patients vs placebo • Statistically significant (p<0.05) improvement in volume in three regions (bottom right) • No significant treatment differences on other key endpoints • Analyses of biomarker and proteomic data to be presented in July SPARC (COG0105) Results MRI Brain Volume (cm 3 ) 6 - mo change from baseline CT1812 (Pooled) Placebo P - value vs placebo Hippocampus - 0.09 (0.08) - 0.40 (0.11) 0.0412 Prefrontal Cortex - 0.41 (0.95) - 4.80 (1.37) 0.0125 Pericentral Cortex 0.07 (0.53) - 2.90 (0.77) 0.0032 First longitudinal study of [ 11 C]UCB - J tracer in AD patients SPARC COG0105 study (NCT03493282) funded by NIA grant RF1AG057553 LS Mean Change from Baseline (cm 3 ) (Mean ± S.E.M.)

13 • Principal investigator: E. Vijverberg , MD, PhD; neurologist at Vumc Alzheimer’s Center • Single - site quantitative EEG study in patients with mild - to - moderate AD • Two group cross over design • Objective: evaluate the efficacy of CT1812 in restoring synaptic function through quantitative EEG, as reflected by relative theta power Assessment of brain wave activity via quantitative EEG SEQUEL (COG0202) Day 0 4 weeks 1:1:1 Study Design (n=16) Placebo (n=8) CT1812 (n=8), 300mg CT1812, 300mg Placebo All doses: QD, oral Day 0 4 weeks SEQUEL COG0202 study (NCT04735536) funded by NIA grant AG058710 Screening: Labs, EEG, exams, MRI Assessments: CSF, EEG Biomarkers: A β, tau, ptau , NFL, neurogranin, synaptotagmin, SNAP25

14 Phase 2 efficacy study, powered to show change in cognition: slowing or halting cognitive decline • Enrolling ~540 patients with early Alzheimer’s disease at ~35 leading academic U.S. sites • Initiation in 2H 2022 • Grant awarded in collaboration with ACTC: premier Alzheimer’s clinical trial group Substantial grant award of $81M funds program Expanded Patient Population: Early AD COG0203 Study funded by NIA grant R01AG065248

15 Identified PD Biomarkers Associated with Alzheimer’s Pathology Normalized by CT1812 in SHINE Biomarkers normalized by CT1812 Most Highly Represented Pathways Pharmacodynamic Biomarkers of CT1812 Discovered M4 Synapse/Neuron M3 Oligo/Myelination M1 Synapse/Neuron M21 MHC Complex/Immune M42 Matrisome M17 Transcription M11 Cell - ECM Interaction M29 Glycosylation/ER M7 MAPK/Metabolism M13 RNA Splicing M2 Mitochondria M16 RNA Binding Downregulated: 74 Upregulated: 52 p<0.05

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:

17 • In the U.S., approximately 13 million people have a form of dementia 1 - Dementia with Lewy bodies (DLB): 1.4 million - PD: 1 million • Direct healthcare costs: - DLB: $31.5 billion 2 - PD: $25 billion 3 Synucleinopathies are 2nd only to AD in Prevalence Parkinson's Disease DLB Alzheimer's Disease Vascular Dementia Frontotemporal Dementia Dementias Estimated US Prevalence 1) Milken Institute report: (2019) Reducing the Cost and Risk of Dementia: Recommendations to Improve Brain Health and Decrease Dis parities. 2) LBDA (extrapolated): LBD is the Most Expensive Dementia in America and Yingjia Chen et al Alzheimers Dement. 2019 3) MJFF and The Lewin Group: Economic Burden and Future Impact of Parkinson's Disease (2019) α - synuclein oligomers, which disrupt key cellular processes, are a hallmark of both disorders

18 σ - 2 Modulators May be Disease Modifying in Synucleinopathies Cellular evidence that σ - 2 modulators have a beneficial impact α - synuclein oligomer - induced trafficking deficits (red) are reversed by Cognition drug (black) Cognition antagonists block the binding / internalization of α - synuclein oligomers at synapses.  - synuclein oligomers  - synuclein oligomers + CT1812  - Synuclein oligomers in red Cognition compounds (black and gray) reverse the effect of α - synuclein oligomers on LAMP2a (orange) Limegrover CS, et al. J Neurosci Res . 2021. doi : 10.1002/jnr.24782

19 • Principal investigator: James E. Galvin, MD, MPH, professor of neurology and director of the Comprehensive Center for Brain Health • Phase 2 trial ongoing • U Miami and 20+ academic sites • Archived DLB R&D educational symposium available: https://ir.cogrx.com DLB Phase 2 Funded with ~$30M NIA Grant Placebo ( n =40) CT1812 100 mg ( n =40) Baseline 6 months CT1812 300 mg ( n =40) 1:1:1 SHIMMER Study (COG1201) Screening: DLB diagnosis MRI ICF for ApoE genotyping LP consent for CSF MMSE: 18 - 27 Assessments: safety, MOCA, CDR, CAF, ESS, MDS - UPDRS III, ADCS - CGIC, ADAS - ADL, NPI CSF - A β, tau, ptau , NFL, neurogranin, synaptotagmin, SNAP25 Intervening visits All doses: QD, oral COG1201 study funded by NIA grant R01AG071643

Dry Age - related Macular Degeneration Cognition Pipeline:

21 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 • Non - invasive oral small molecule approach to reach retina • Clinical biomarker support : Proteomics analyses showed differential movement of proteins involved in dry AMD • Preclinical data: regulates cell survival and inflammatory pathways, ameliorate trafficking deficits Rationale for σ - 2 Modulators in Dry AMD RPE Cell σ - 2 receptors Oxidative stress σ - 2 modulators Goal: Protect RPE Cells From Disease - relevant Stressors A β oligomers Inflammation

22 • Aβ oligomers and oxidative stress cause lysosomal deficits in capacity to traffic & degrade photoreceptor outer segments (POS) cargos in RPE cells • σ - 2 receptor modulators from 3 chemically distinct series rescued these deficits Results: σ - 2 Receptor Modulators Prevent Deficits in Trafficking / Degradation of POS from 2 Insults 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) P O S i n L C 3 B + a u t o p h a g y b o d i e s * * 12 24 36 48 0.0 0.2 0.4 0.6 0.8 1.0 Time (hr) P O S i n L C 3 B + a u t o p h a g y b o d i e s * * * Control A β oligomers H 2 O 2 Stressor+CT1812

23 Genetic, Clinical Biomarker and Preclinical Data Support Moving Forward with CT1812 for dAMD * Subject to discussion with FDA Assessments such as: Change in GA lesion Low luminance visual acuity (LLVA) Best - corrected visual acuity (BCVA) Study Drug Administration Screening: Age: ≥ 50 Diagnosis of dry AMD BCVA ≥ 24 letters (ETDRS) GA lesion ≥ 2.5 and ≤17.5mm 2 0 mo 3 mo 6 mo 9 mo 12 mo Placebo (n≈100) CT1812 (n ≈ 100) Planned Phase 2* will assess CT1812 in patients with diagnosed dry AMD and measurable GA 1:1 Orally administered CT1812 reaches the target tissue at >80% RO

Financial Position Financials as of March 31, 2022 • Cash and Cash Equivalents: $52.5 million • Proceeds raised from IPO: $52.0 million • Sufficient cash runway into 2H 2023 NIA funding for CT1812 studies as of Dec 31, 2021 • Preclinical through Phase 2 studies $168.4 million • Approximate funding used ($58.0 million) - Available NIA funding $110.4 million

Thank You James O’Brien Chief Financial Officer 203 - 536 - 1797 jobrien@cogrx.com Lisa Ricciardi President & CEO 917 - 658 - 5789 lricciardi@cogrx.com

26 Membrane Trafficking Screening Assay Novel phenotypic screening assay - Neurons - A β oligomer toxin - Membrane trafficking readout Novel proprietary chemical library More than 10k compounds screened Candidate identification and development 5 distinct chemical series, each with 100s of analogues CT1812, CT2168 CT2047, CT2638 SAR MedChem σ - 2 modulators ​