Slide 1: Results from the Proof-of-Concept Phase 2 SHINE Study of CT1812 in Mild-to-Moderate Alzheimer's Disease
Results from the Proof-of-Concept Phase 2 ‘SHINE’ Study of CT1812 in Mild-to-Moderate Alzheimer’s Disease July 29, 2024
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: Alzheimer's Disease and CGTX
3 Alzheimer’s Disease and CGTX CGTX SOLUTION Lead asset is CT1812: An investigational oral small molecule that potently antagonizes amyloid oligomers via a unique mechanism of action ✓ Completed: Phase 2 POC SHINE trial in Mild-to-Moderate Alzheimer’s disease population ✓ Phase 2 POC dementia with L
Slide 4: Agenda for SHINE Study Presentation
4 • Development History of CT1812 • Results of Cognitive and Functional Measures • Safety and Tolerability • Exploratory Biomarker Findings • Commentary – Dr. Martin Sadowski • Questions and Answers Agenda for SHINE Study Presentation
Slide 5: Today's Speakers
5 Martin J. Sadowski, M.D., Ph.D. Professor of Neurology, Psychiatry, Biochemistry and Molecular Pharmacology at NYU Director of the Alzheimer Drug Trial Program Study investigator and industry thought leader Today’s Speakers Everard (Jort) Vijverberg, MD, PhD Staff Neurologist and CNS Trial Special
Slide 6: CT1812 Background: Brief history of CT1812 development
6 • Candidate identified by Cognition Therapeutics team via a screen established to identify molecules that protect neurons from the toxicity of Aβ oligomers • Long history of Cognition research and publications has demonstrated that CT1812 can reduce the binding affinity of Aβ oligomers • All intel
Slide 7: Summary of COG0201 SHINE Results
7 • COG0201 SHINE: FPI October 2018, LPO May 2024 • Favorable treatment differences versus placebo with both 100mg and 300mg dose groups on all key cognitive outcome measures • CT1812 treatment resulted in slowing progression across outcome measures - The magnitude of effect is comparable to approve
Slide 8: SHINE COG0201 Study Design
8 Phase 2 Safety and Efficacy Study in Adults with Mild-to-Moderate Alzheimer’s Disease SHINE COG0201 study (NCT03507790) partially funded by $31M NIA grant R01AG058660
Slide 9: COG0201 SHINE Participant Disposition
9 COG0201 SHINE Participant Disposition
Slide 10: COG0201 SHINE Baseline Characteristics
10 COG0201 SHINE Baseline Characteristics
Slide 11: Cognitive Endpoints: ADAS-Cog 11 and MMSE
11 39% slowing of ADAS-Cog 11 decline at six months vs baseline compared to placebo, magnitude of effect similar to approved MAbs Cognitive Endpoints: ADAS-Cog 11 and MMSE ADAS-Cog 11 MMSE
Slide 12: Cognitive Endpoints: ADAS-Cog 13, Cognitive Composite
12 Cognitive Endpoints: ADAS-Cog 13, Cognitive Composite Consistent results across multiple cognitive endpoints ADAS-Cog 13 Cognitive Composite
Slide 13: Additional Cognitive and Functional Measures
13 Additional Cognitive and Functional Measures Consistent though not significant results; likely requires longer-term trial ADCS-ADL ADCS-CGIC
Slide 14: Summary of Exploratory Outcomes
14 Summary of Exploratory Outcomes Trending positive across most cognitive and functional measures Time Frame ADAS-Cog 11 ADAS-Cog 13 ADCS-CGIC ADCS-ADL Cognitive Composite MMSE CT1812 100mg Day 98 Δ -1.79 p = 0.0430 Δ -2.16 p =0.0376 Δ 0.11 p = 0.6288 Δ 0.05 p = 0.9644 Δ 0.05 p = 0.3920 Δ 0.97 p =
Slide 15: Summary Exploratory Outcomes - Percent Slowing
15 Summary Exploratory Outcomes - Percent Slowing Day 182 Effect as large or larger than approved MAbs and some experimental therapeutics ADAS-Cog 11 ADAS-Cog 13 MMSE Cognitive Composite ADCS-ADL ADCS-CGIC CT1812 100mg 36% 42% 47% 40% 28% 32% CT1812 300mg 40% 36% 93% 60% 23% 24% CT1812 Pooled 39% 39
Slide 16: Safety Findings
Safety Findings COGNITION” Therapeutics
Slide 17: COG0201 SHINE TEAE Summary
17 Adverse events are well balanced and mostly mild or moderate in nature COG0201 SHINE TEAE Summary
Slide 18: Most Frequent AEs
18 Most Frequent AEs Reported by system organ class and preferred term
Slide 19: COG0201 SHINE Safety Conclusions
19 • CT1812 demonstrated favorable safety and tolerability profile • Most AEs were mild or moderate • Percentage of subjects experiencing any AE was similar between the pooled CT1812 treatment group (76.5%) and the placebo group (78%) • Serious AE rates were 4.9% among CT1812 subjects and 10% among
Slide 20: Exploratory Biomarker Findings
Exploratory Biomarker Findings
Slide 21: Biomarkers of Synaptic Function: Biomarker Findings
21 • CSF samples at screening and Day 182 (optional), available in ~50% of mITT population • Neurofilament Light Chain - Significant (p<0.05) reduction relative to placebo for 300mg dose - Reduction trend (p<0.10) for 100mg dose - Supports potential slowing of neurodegeneration • No change in Aβ42/4
Slide 22: Signal of Impact on Neurodegeneration Based on NfL Change
22 Reductions in CSF NfL relative to placebo consistent with slowing neurodegeneration Signal of Impact on Neurodegeneration Based on NfL Change
Slide 23: What We Have Learned from POC SHINE Phase 2 Trial
23 • CT1812 showed favorable safety and tolerability profile with most AEs mild or moderate • Results of study inform dosing for next phase of study - 100mg dose provided similar efficacy to 300mg dose - At 100mg, no discontinuations due to AEs • Consistent efficacy signal: favorable, non-statistica
Slide 24: Science & Clinical Medicine Advance Through the Work of Many
24 • Participants and their study partners • Clinical investigators and site staff • US and International Clinical research partners • Cognition clinical operations team • Funding partners including our investors, NIA/NIH and ADDF CGTX wishes to acknowledge and thank those who made this trial possib
Slide 25: Remarks from Dr. Martin Sadowski, followed by Question and Answers
Remarks from Dr. Martin Sadowski, followed by Question and Answers
Slide 26: Thank You
Thank You Lisa Ricciardi President & CEO lricciardi@cogrx.com Tony Caggiano, MD, PhD CMO and Head of R&D acaggiano@cogrx.com John Doyle Chief Financial Officer jdoyle@cogrx.com