8-K
Cognition Therapeutics Inc (CGTX)
8-K
2022-08-29
For: 2022-08-29
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UNITED
STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549
FORM 8-K
CURRENT REPORTPursuant to Section 13 or 15(d)of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): August 29, 2022
CognitionTherapeutics, Inc.(Exact name of registrant as specified in its charter)
| Delaware | 001-40886 | 13-4365359 |
|---|---|---|
| (State or other jurisdiction of<br><br>incorporation or organization) | (Commission<br>File Number) | (I.R.S. Employer<br><br>Identification No.) |
| 2500 Westchester AvenuePurchase, NY | 10577 | |
| --- | --- | |
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code:
(412) 481-2210
Not
Applicable (Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|---|---|
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of Each Class | Trading Symbol | Name of Exchange on WhichRegistered |
|---|---|---|
| Common Stock, par value $0.001 per share | CGTX | The Nasdaq Stock Market LLC |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
Item 7.01 Regulation FD Disclosure.
Attached as Exhibit 99.1 and furnished for purposes of Regulation FD is a presentation that Cognition Therapeutics, Inc. may use from time to time in presentations or discussions with investors, analysts, and other parties.
The information in this Item 7.01 (including Exhibit 99.1) is being furnished solely to satisfy the requirements of Regulation FD and shall not be deemed to be “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, nor shall it be deemed to be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
The following exhibit is being furnished herewith:
| Exhibit No. | Document |
|---|---|
| 99.1 | Investor presentation of Cognition Therapeutics, Inc. |
| 104 | Cover Page Interactive<br> Data File (embedded within the Inline XBRL document). |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| COGNITION THERAPEUTICS, INC. | |
|---|---|
| By: | /s/ Lisa Ricciardi |
| --- | --- |
| Name: | Lisa Ricciardi |
| Title: | President and Chief Executive Officer |
Date: August 29, 2022
Exhibit 99.1
| Developing disease-<br>modifying medicines for<br>degenerative disorders<br>August 2022 |
|---|
| 2<br>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<br>statements that relate to present facts or current conditions, including but not limited to, statements regarding our cash and financial resources and our clinical development plans, are forward-looking statements. These<br>statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or<br>achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,”<br> “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. We have based these forward-looking<br>statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking<br>statements speak only as of the date of this presentation and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control.<br>Factors that may cause actual results to differ materially from current expectations include, but are not limited to: competition, our ability to secure new (and retain existing) grant funding, our ability to grow and manage<br>growth, maintain relationships with suppliers and retain our management and key employees; our ability to successfully advance our current and future product candidates through development activities, preclinical studies<br>and clinical trials and costs related thereto; the timing, scope and likelihood of regulatory filings and approvals, including regulatory approval of our product candidates; changes in applicable laws or regulations; the possibility<br>that the we may be adversely affected by other economic, business or competitive factors; our estimates of expenses and profitability; the evolution of the markets in which we compete; our ability to implement our strategic<br>initiatives and continue to innovate our existing products; our ability to defend our intellectual property; the impact of the COVID-19 pandemic on our business, supply chain and labor force; and the risks and uncertainties<br>described in the “Risk Factors” section of our annual and quarterly reports filed the Securities Exchange Commission. You should not rely on these forward-looking statements as predictions of future events. The events and<br>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<br>industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable<br>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.<br>TRADEMARKS<br>This presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks,<br>trade names and copyrights referred to in this presentation may be listed without the TM, SM © or ® symbols, but we will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these<br>trademarks, service marks, trade names and copyrights.<br>MARKET & INDUSTRY DATA<br>Projections, estimates, industry data and information contained in this presentation, including the size of and growth in key end markets, are based on information from third-party sources and management estimates.<br>Although we believe that these third party-sources are reliable, we cannot guarantee the accuracy or completeness of these sources. Our management’s estimates are derived from third-party sources, publicly available<br>information, our knowledge of our industry and assumptions based on such information and knowledge. Our management’s estimates have not been verified by any independent source. All of the projections, estimates,<br>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<br>assumptions relating to us and our industry's future performance 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<br>cause future performance to differ materially from our expressed projections, estimates and assumptions or those provided by third parties.<br>Forward-looking Statement |
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| 3<br>Who We Are<br>Targeting unmet needs in age-related degenerative disorders of the central nervous system and retina<br>such as Alzheimer’s disease, dementia with Lewy bodies (DLB), dry age-related macular degeneration<br>(dry AMD), and Parkinson’s disease<br>Functionally distinct therapeutic approach focused on the sigma-2 (σ-2) receptor complex, backed by<br>decades of expertise in the biology of synaptic function and plasticity<br>Received over $160 million in non-dilutive grant funding through key collaborations with the National<br>Institute of Aging and other thought-leading institutions<br> − Approximately 50% of ongoing R&D expenses covered by grants<br>Multiple Phase 2 programs expected to provide significant value-creating milestones and data readouts<br>over the next 12 to 24 months<br>Expanding pipeline through our proprietary NICE screening platform, strategic alliances and acquisitions<br>Seasoned management team with broad scientific, drug development and commercial expertise;<br>experienced board and advisors |
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| 4<br>Product<br>Candidate<br>Target<br>Indication Preclinical Phase 1 Phase 2 Phase 3 Funding<br>CT1812 SEQUEL<br>Mild-moderate AD $3.3M<br>CT1812 SHINE<br>Mild-moderate AD $30M<br>CT1812 SHIMMER<br>DLB $30M<br>CT1812 START<br>Early-stage AD $81M<br>CT1812 Dry AMD<br>CT2168 Synucleinopathies †<br>CT2074 Dry AMD<br>Pipeline<br> † including Parkinson’s disease and DLB<br>IND enabling studies<br>IND enabling studies<br>Please note: CT1812 and other pipeline candidates are not approved for use in the US or other jurisdictions |
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| 5<br>Clinical Study Total Awarded Remaining<br>(yet to be drawn down)<br>START (early AD) $ 81 Million $ 65.1 Million<br>SHINE (mild/mod AD) $ 30.5 Million $ 11 Million<br>SHIMMER (DLB) $ 29.5 Million $ 20.5 Million<br>SEQUEL (qEEG in AD) $ 3.3 Million $ 0.4 Million<br>$ 144.3 Million $ 97 Million<br>Approximately 50% of R&D Funded by Grants<br>Grants Continue to Provide Funding<br>NOTE: figures are approximate dollar amounts as June 30, 2022 |
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| 6<br>2021 2022 2023<br>Completing<br> • PK<br> • Human AME<br> • SEQUEL<br>Conducting<br> • SHINE (cohort 2)<br> • Phase 2 in DLB<br> • Phase 2 with ACTC<br> • Phase 2 in dry AMD<br> • IND-enabling studies for research compounds<br>Key Upcoming Milestones & Expected Timing<br>Completed<br> ✓ SNAP<br> ✓ SPARC<br> ✓ SHINE (cohort 1)<br>Completing<br> • SHINE (cohort 2)<br>Ongoing Studies<br> • Phase 2 in DLB<br> • Phase 2 with ACTC<br> • Phase 2 in dry AMD<br>Regulatory Actions<br> • IND filings for pipeline compounds |
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| Review of CT1812 for the Treatment<br>of Alzheimer’s Disease<br>Cognition Lead Program: |
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| 8<br> • Approx. 6.2 million individuals in United<br>States are afflicted with Alzheimer’s disease1<br>- Approximately 35 million people worldwide2<br>- Prevalence expected to double by 20501<br> • Direct healthcare costs for patients with<br>Alzheimer’s and other dementias is<br>estimated to exceed $300 billion in the<br>United States alone1<br>- Projected to increase to $1+ trillion by 20501<br>Mild,<br>50.4%<br>Moderate,<br>30.3%<br>Severe,<br>19.3%<br>Stages of Disease Afflicting Current<br>Population of Alzheimer’s Patients<br>Alzheimer’s Disease Market Overview<br>1) Economic Burden of Alzheimer Disease and Managed Care Considerations. Am J Manag Care. 2020;26:S177-S183<br>2) World Health Organization Key Facts: Dementia |
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| 9<br> • CT1812 penetrates the blood-brain<br>barrier (BBB) and binds selectively to the<br> σ-2 receptor<br> • By modulating σ-2, CT1812 displaces<br>and prevents oligomers from binding to<br>neurons and clears them into CSF<br> • Prevents synaptotoxicity and facilitates<br>restoration of neuronal function<br> • CT1812 mimics the protective effects of<br>the A673T-APP “Icelandic” mutation<br>CT1812: A Synaptoprotective Approach to Alzheimer’s Disease<br> • 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<br> • 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<br> • 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<br> • 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<br> σ-2<br>modulator<br>Oligomer<br>receptor<br>Neuronal<br>Synapse<br> σ-2<br>receptors<br>Aβ<br>oligomers |
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| 10<br>Evidence of Target Engagement: SNAP (COG0104)<br>First evidence of target engagement in humans, mirrors preclinical findings, corroborating our mechanism of action<br> …and now in people with Alzheimer’s<br>disease<br>CT1812<br>oligomer receptor<br>complex<br>PGRMC1<br> σ-2 receptor<br>complex<br>TMEM97<br>This displacement can be measured in the<br>CSF in Alzheimer’s mice treated with CT1812<br>CT1812 mechanism of action: By binding to<br>the σ-2 receptor, CT1812 displaces Aβ<br>oligomers from synapses, thus preventing<br>synaptic toxicity<br>0 10 20 30<br>0<br>200<br>400<br>600<br>MIE Measurement - Patient 1<br>Hrs<br>%<br><br>C<br>h<br>a<br>n<br>g<br>e<br><br>a<br>b<br>o<br>v<br>e<br><br>b<br>a<br>s<br>e<br>l<br>i<br>n<br>e<br>0 10 20 30<br>0<br>200<br>400<br>600<br>MIE Measurement - Patient 2<br>Hrs<br>%<br><br>C<br>h<br>a<br>n<br>g<br>e<br><br>a<br>b<br>o<br>v<br>e<br><br>b<br>a<br>s<br>e<br>l<br>i<br>n<br>e<br>0 10 20 30<br>0<br>200<br>400<br>600<br>MIE Measurement - Patient 3<br>Hrs<br>%<br><br>C<br>h<br>a<br>n<br>g<br>e<br><br>a<br>b<br>o<br>v<br>e<br><br>b<br>a<br>s<br>e<br>l<br>i<br>n<br>e<br>MIE Measurement – CT1812 (n=1)<br>Dose administration<br>hours<br>% change ABOs in CSF v baseline<br>0 10 20 30<br>0<br>200<br>400<br>600<br>MIE Measurement - Patient 1<br>Hrs<br>%<br><br>C<br>h<br>a<br>n<br>g<br>e<br><br>a<br>b<br>o<br>v<br>e<br><br>b<br>a<br>s<br>e<br>l<br>i<br>n<br>e<br>0 10 20 30<br>0<br>200<br>400<br>600<br>MIE Measurement - Patient 2<br>Hrs<br>%<br><br>C<br>h<br>a<br>n<br>g<br>e<br><br>a<br>b<br>o<br>v<br>e<br><br>b<br>a<br>s<br>e<br>l<br>i<br>n<br>e<br>0 10 20 30<br>0<br>200<br>400<br>600<br>MIE Measurement - Patient 3<br>Hrs<br>%<br><br>C<br>h<br>a<br>n<br>g<br>e<br><br>a<br>b<br>o<br>v<br>e<br><br>b<br>a<br>s<br>e<br>l<br>i<br>n<br>e<br>MIE Measurement - Placebo (n=1)<br>hours<br>Dose administration<br>% change ABOs in CSF v baseline<br>minutes<br>MIE Measurement – Vehicle (n=5)<br>Dose administration<br>% Basal CSF A<br> β<br>O<br>MIE Measurement – CT1812 (n=5)<br>Dose administration<br>-20<br>-10 0 10 20 30 40 50 60 70 80 90<br>100<br>110<br>120<br>50<br>100<br>150<br>200<br>250<br>10000<br>20000<br>30000<br>AO in Lateral Ventricle (CSF)<br>Time from Treatment (min)<br>%<br><br>B<br>a<br>s<br>a<br>l<br><br>C<br>S<br>F<br><br>A<br><br>O<br>300<br>minutes<br>% Basal CSF A<br> β<br>O<br>Izzo, NJ et al. Alzheimer's Dement. 2021; 17: 1365-1382.<br>https://doi.org/10.1002/alz.12302<br>SNAP COG0104 study (NCT03522129)<br>funded by NIA grant 1RF1AG057780 |
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| 11<br> • Trend towards slower cognitive decline in<br>CT1812-treated vs placebo-treated<br>participants as measured by ADAS-Cog 11<br>Cognitive & Biological Outcomes<br> • Statistically significantly lower Aβ protein<br>(p=0.017) in treated vs placebo patients<br> • Additional analyses on p-tau, synaptic and<br>AD-related proteins ongoing<br>Placebo<br>CT1812 100 mg<br>Day 0 6 months<br>1:1:1<br>Study Design (n=144)<br>Screening:<br>Labs, exams, MRI,<br>brain amyloid PET<br>Assessments:<br>Cognitive testing,<br>Biomarkers (CSF/Plasma)<br>CT1812 300 mg<br>SHINE interim analysis (n=24) yields promising evidence<br>All doses: QD, oral<br>SHINE COG0201 study (NCT03507790)<br>funded by NIA grant R01AG058660 |
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| 12<br>Biomarkers Associated with Alzheimer’s Pathology<br>Normalized by CT1812<br>Biomarkers normalized<br>by CT1812<br>Most Highly<br>Represented Pathways<br>Pharmacodynamic Biomarkers<br>of CT1812 Discovered<br>M4 Synapse/Neuron<br>M3 Oligo/Myelination<br>M1 Synapse/Neuron<br>M21 MHC Complex/Immune<br>M42 Matrisome<br>M17 Transcription<br>M11 Cell-ECM Interaction<br>M29 Glycosylation/ER<br>M7 MAPK/Metabolism<br>M13 RNA Splicing<br>M2 Mitochondria<br>M16 RNA Binding<br>Downregulated:<br>74<br>Upregulated:<br>52<br>p<0.05<br>Log2 abundance |
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| 13<br>1° Endpoints:<br> • Impact of CT1812 on synaptic density as measured<br>by SV2A; safety and tolerability<br>Results:<br> • No difference in synaptic density in CT1812- or<br>placebo-treated vs baseline<br> • Trend towards preservation of brain volume<br>(composite) in CT1812- vs placebo-treated<br>- Statistically significant (p<0.05) improvement in<br>volume in three regions (bottom right)<br> • Adverse event profile consistent with prior studies<br>- Elevated liver enzymes resolved upon<br>discontinuation of study drug<br>- No serious TEAEs were reported<br>SPARC (COG0105) Results<br>MRI Brain Volume (cm3)<br>6-mo change from baseline<br>CT1812 (Pooled) Placebo P-value vs<br>placebo<br>Hippocampus -0.09 (0.08) -0.40 (0.11) 0.0412<br>Prefrontal Cortex -0.41 (0.95) -4.80 (1.37) 0.0125<br>Pericentral Cortex 0.07 (0.53) -2.90 (0.77) 0.0032<br>SPARC COG0105 study (NCT03493282) funded by NIA grant RF1AG057553<br>LS Mean Change from Baseline (cm<br>3<br>)<br>(Mean<br> ±<br>S.E.M.) |
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| 14<br> • 37 proteins in CSF were significantly (p<0.05) normalized<br>towards control with CT1812 compared to placebo<br> • These proteins are involved in key pathways disrupted in<br>Alzheimer’s: autophagy, inflammation, synaptic function<br>- Include previously well-characterized biomarkers of Alzheimer's<br>disease, such as YKL-40 and genetic risk factors for Alzheimer's<br>disease such as clusterin<br> • Analyses support targeting σ-2 receptor with CT1812<br>Proteomic Data from SPARC Shows Effect of CT1812 on<br>Disrupted Alzheimer’s Disease Processes<br>NOTE: proteomic analyses conducted on 18 SPARC participants for whom there were CSF samples at baseline and at end of study |
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| 15<br>-2.50<br>-2.00<br>-1.50<br>-025<br>000<br>025<br>050<br>075<br>200<br>250<br>300<br>350<br>PLXDC2<br>PRSS23<br>PCYOX1<br>F13A1<br>RNASE6<br>RNASE4<br>VASN<br>SOD3<br>ANG<br>WFIKKN2<br>SLPI<br>MERTK<br>APOL1<br>LRP1<br>PLD3<br>CD5L<br>IGLV8-61<br>IGLV3-25<br>IGLV3-16<br>ARG1<br>B2M<br>SMOC1<br>C1R<br>IGHD<br>IGHM<br>COL6A2<br>VCAN<br>ADARB1<br>CALB2<br>LAMP2<br>LAMP1<br>IGFBP2<br>OLFML3<br>ALDOC<br>SPON1<br>CHI3L1<br>DTD1<br>log2 abundance<br>Immune System/<br>Inflammatory<br>response<br>Regulation of Peptidase Activity<br>Lipid Metabolic Process<br>Oxidative Stress<br>Autophagy<br>Other<br>Complement<br>Cell Adhesion<br>RNA metabolic<br>process<br>Synaptic Transmission<br>Extracellular Matrix<br>Phagocytosis<br>AD Biomarkers<br>**<br>*<br>*<br>*<br>Log2 FC<br>increased decreased<br>Biomarkers normalized<br>by CT1812<br>Biomarkers of CT1812 Identified, Several of Which May<br>Reflect Disease Modification<br>AD vs. control (red)<br>CT1812 vs placebo (blue)<br> = AD Priority Biomarker<br> = Mapped to Top 5 Brain Module<br>NOTE: proteomic analyses conducted on 18 SPARC participants for whom there were CSF samples at baseline and at end of study<br>M3 Oligo / Myelination<br>M26 Complement / Acute Phase<br>M7 MAPK / Metabolism<br>M4 Synapse / Neuron<br>M1 Synapse / Neuron<br>M14 Protein Folding<br>M21 MHC Complex / Immune<br>M27 Extracellular Matrix<br>Most Highly Represented<br>Pathways<br>Pharmacodynamic Biomarkers<br>of CT1812 Discovered<br>CHI3L1 (YKL-40) = inflammatory protein in Alzheimer’s disease<br>SMOC1 = Aβ plaque-associated protein in Alzheimer’s disease<br>CLU = Alzheimer’s disease genetic risk factor (clusterin; APOJ) |
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| 16<br> • Principal investigator: E. Vijverberg, MD, PhD;<br>neurologist at Vumc Alzheimer’s Center<br> • Single-site quantitative EEG study in patients<br>with mild-to-moderate AD<br> • Two group cross over design<br> • Objective: evaluate the efficacy of CT1812 in<br>restoring synaptic function through<br>quantitative EEG, as reflected by relative<br>theta power<br>Assessment of brain wave activity via quantitative EEG<br>SEQUEL (COG0202)<br>Day 0 4 weeks<br>1:1:1<br>Study Design (n=16)<br>Placebo (n=8)<br>CT1812 (n=8), 300mg<br>CT1812, 300mg<br>Placebo<br>Day 0 4 weeks<br>SEQUEL COG0202 study (NCT04735536) funded by NIA grant RF1AG058710<br>Screening:<br>Labs, EEG, exams, MRI<br>Assessments:<br>CSF, EEG<br>Biomarkers: Aβ, tau, ptau, NFL,<br>neurogranin, synaptotagmin, SNAP25<br>Oral QD Administration |
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| 17<br> • Phase 2 efficacy study, powered to show<br>change in cognition: slowing or halting<br>cognitive decline<br> • Enrollment expected to commence 2H 2022<br> • Enrolling 540 participants with early<br>Alzheimer’s disease at 50-60 U.S. sites<br> • Supported by $81M Grant from NIA<br>- Grant awarded in collaboration with ACTC:<br>premier Alzheimer’s clinical trial group<br>Substantial grant award of $81M funds program<br>Patient Population: Early AD<br>COG0203 Study funded by NIA grant R01AG065248<br>START Trial Schematic<br>Screening<br>Labs, exams<br>CT1812 100 mg (n=180)<br>Placebo (n=180)<br>CT1812 300 mg (n=180)<br>Oral QD Administration<br>NIH<br>NIA |
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| Synucleinopathies<br>Disorders such as DLB and Parkinson’s<br>disease that are characterized by<br>deposits of α-synuclein aggregates<br>(called Lewy bodies) that disrupt key<br>cellular processes<br>Cognition Pipeline: |
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| 19<br> • In the U.S., approximately 13 million people<br>have a form of dementia1<br>- Dementia with Lewy bodies (DLB): 1.4 million<br>- PD: 1 million<br> • Direct healthcare costs:<br>- DLB: $31.5 billion2<br>- PD: $25 billion3<br>Synucleinopathies are 2nd only to AD in Prevalence<br>Parkinson's<br>Disease<br>DLB<br>Alzheimer's<br>Disease<br>Vascular<br>Dementia<br>Frontotemporal<br>Dementia<br>Dementias<br>Estimated US Prevalence<br>1) Milken Institute report: (2019) Reducing the Cost and Risk of Dementia: Recommendations to Improve Brain Health and Decrease Disparities.<br>2) LBDA (extrapolated): LBD is the Most Expensive Dementia in America and Yingjia Chen et al Alzheimers Dement. 2019<br>3) MJFF and The Lewin Group: Economic Burden and Future Impact of Parkinson's Disease (2019)<br> α-synuclein oligomers, which disrupt key cellular processes, are a hallmark of both disorders |
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| 20<br> σ-2 Modulators May be Disease Modifying in Synucleinopathies<br>Cellular evidence that σ-2 modulators have a beneficial impact<br> α-synuclein oligomer-induced trafficking deficits<br>(red) are reversed by Cognition drug (black)<br>Cognition antagonists block the binding /<br>internalization of α-synuclein oligomers<br>at synapses<br>;-synuclein oligomers<br>;-synuclein oligomers<br>+ CT1812<br>;-Synuclein oligomers in red<br>Cognition compounds (black<br>and gray) reverse the effect of<br> α-synuclein oligomers on<br>LAMP2a (orange)<br>Limegrover CS, et al. J Neurosci Res. 2021. doi: 10.1002/jnr.24782 |
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| 21<br> • Principal investigator: James E. Galvin, MD,<br>MPH, professor of neurology and director of<br>the Comprehensive Center for Brain Health<br> • Phase 2 trial ongoing<br>- Participant dosing underway<br> • U Miami and 20+ academic sites<br> • Archived DLB R&D educational symposium<br>available: https://ir.cogrx.com<br>DLB Phase 2 Funded with ~$30M NIA Grant<br>Placebo (n=40)<br>CT1812 100 mg (n=40)<br>Baseline 6 months<br>CT1812 300 mg (n=40)<br>1:1:1<br>SHIMMER Study (COG1201)<br>Screening:<br>DLB diagnosis<br>MRI<br>ICF for ApoE genotyping<br>LP consent for CSF<br>MMSE: 18-27<br>Assessments:<br>safety, MOCA, CDR, CAF, ESS, MDS-<br>UPDRS III, ADCS-CGIC, ADAS-ADL, NPI<br>CSF -Aβ, tau, ptau, NFL, neurogranin,<br>synaptotagmin, SNAP25<br>Intervening visits<br>All doses: QD, oral<br>COG1201 study partially funded by NIA grant R01AG071643 |
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| Dry Age-related Macular Degeneration<br>Cognition Pipeline: |
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| 23<br> σ-2 receptors<br> • Expression: in RPE cells, retinal ganglion cells,<br>photoreceptors in retina<br> • Biology: Regulates autophagy, protein trafficking, lipid<br>metabolism dysregulated in AMD<br> • Target validation: TMEM97 knockdown is protective<br> • Human genetics: Linked to dry AMD<br> σ-2 receptor modulators<br> • Non-invasive oral small molecule approach to reach retina<br> • Clinical biomarker support: Proteomics analyses showed<br>differential movement of proteins involved in dry AMD<br> • Preclinical data: regulates cell survival and inflammatory<br>pathways, ameliorate trafficking deficits<br>Rationale for σ-2 Modulators in Dry AMD<br>RPE Cell<br> σ-2<br>receptors<br>Oxidative<br>stress<br> σ-2<br>modulators<br>Goal: Protect RPE Cells From Disease-relevant Stressors<br>Aβ<br>oligomers<br>Inflammation |
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| 24<br> • Aβ oligomers and oxidative stress cause lysosomal deficits in capacity to<br>traffic & degrade photoreceptor outer segments (POS) cargos in RPE cells<br> • σ-2 receptor modulators from 3 chemically distinct series rescued these deficits<br>Results: σ-2 Receptor Modulators Prevent Deficits in<br>Trafficking / Degradation of POS from 2 Insults<br>Receptor-bound POS<br>Lysosome<br>(LAMP 1/2)<br>Autophagy<br>Body (LC3b)<br>Early Compartment<br>(Rab 5)<br>Rab 7<br>12 24 36 48<br>0.0<br>0.2<br>0.4<br>0.6<br>0.8<br>1.0<br>Time (hr)<br>P<br>O<br>S<br><br>i<br>n<br><br>L<br>C<br>3<br>B<br>+<br>a<br>u<br>t<br>o<br>p<br>h<br>a<br>g<br>y<br><br>b<br>o<br>d<br>i<br>e<br>s *<br>*<br>12 24 36 48<br>0.0<br>0.2<br>0.4<br>0.6<br>0.8<br>1.0<br>Time (hr)<br>P<br>O<br>S<br><br>i<br>n<br><br>L<br>C<br>3<br>B<br>+<br>a<br>u<br>t<br>o<br>p<br>h<br>a<br>g<br>y<br><br>b<br>o<br>d<br>i<br>e<br>s<br>*<br>*<br>*<br>Control<br>Aβ oligomers<br>H2O2<br>Stressor+CT1812 |
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| 25<br>Genetic, Clinical Biomarker and Preclinical Data Support<br>Moving Forward with CT1812 for dAMD<br>Assessments such as:<br>Change in GA lesion<br>Low luminance visual acuity (LLVA)<br>Best-corrected visual acuity (BCVA)<br>Study Drug Administration<br>Screening:<br>Age: ≥ 50<br>Diagnosis of dry AMD<br>BCVA ≥ 24 letters (ETDRS)<br>GA lesion ≥ 2.5 and ≤17.5mm2<br>0 mo 3 mo 6 mo 9 mo 12 mo<br>Placebo (n≈100)<br>CT1812 (n≈100)<br>Planned Phase 2 will assess CT1812 in patients<br>with diagnosed dry AMD and measurable GA<br>1:1<br>Orally administered CT1812 reaches<br>the target tissue at >80% RO |
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| Financial Position<br>Financials as of June 30, 2022<br> • Cash and Cash Equivalents: $45.8 million<br> • Proceeds raised from IPO: $52.0 million<br> • Expected cash runway into 2H 2023<br>NIA funding for CT1812 studies as of June 30, 2022<br> • Preclinical through Phase 2 studies $168.4 million<br> • Approximate funding used ($70.4 million)<br>- Remaining NIA funding $98.0 million |
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| Thank You<br>Andy Einhorn<br>Interim CFO<br>973-879-8240<br>aeinhorn@cogrx.com<br>Lisa Ricciardi<br>President & CEO<br>917-658-5789<br>lricciardi@cogrx.com |
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