Slide 1: Forward-Looking Statements
1 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 2: Topline Results Phase 2 Study of CT1812 in Mild-to-Moderate Dementia with Lewy Bodies
Topline Results Phase 2 Study of CT1812 in Mild-to-Moderate Dementia with Lewy Bodies December 18, 2024
Slide 3: James E. Galvin, MD, MPH
Director of the Comprehensive Center for Brain Health University of Miami Miller School of Medicine Director at Large of the LBDA Board of Directors and member of the Scientific Advisory Council James E. Galvin, MD, MPH
Slide 4: Dementia with Lewy Bodies (DLB)
4 • 2nd most common cause of dementia after Alzheimer’s disease • Characterized by cognitive impairment that precedes development of motor symptoms • More common in men • Patients may have faster decline than Alzheimer’s • Patients often require several physician visits over 18 months before being c
Slide 5: Four Symptom Domains Drive Lewy Body Disease Burden
5 “A multifactorial disease with a buffet of symptoms” Four Symptom Domains Drive Lewy Body Disease Burden Behavior Cognition Function Movement Patient symptom hallucinations, anxiety, delusions Memory and problem solving Bathing, toileting, shopping, meal preparation Standing, maintaining balance A
Slide 6: SHIMMER Study Designed to Assess Multifactorial Burden
6 SHIMMER Study Designed to Assess Multifactorial Burden Conducted in Collaboration with LBDA Centers of Excellence, Academic Centers and Industry SHIMMER COG1201 study (NCT05225415) partially funded by $30M NIA grant R01AG071643 Key Enrollment Criteria Treatment Period 6 months Assessments Study Ob
Slide 7: Up to 91% Percent Slowing on Assessments
7 Up to 91% Percent Slowing on Assessments Strong clinical signals across major DLB symptoms relative to placebo * Measure of the distress experienced by the care partners of SHIMMER participants Behavior Cognition Function Movement NPI (total) NPI (distress) CDR (episodic memory) MoCA CAF ADCS-ADL
Slide 8: CT1812 Showed Dramatic 82% Impact on Neuropsychiatric Measures
8 CT1812 Showed Dramatic 82% Impact on Neuropsychiatric Measures NPI captures a variety of patient disturbances, including hallucinations, anxiety, and delusions -4 -2 0 2 4 6 0 NPI Total (ITT) CT1812 Pooled Placebo Baseline Day 28 Day 98 Day 182 worsening NPI favor Treatment with CT1812 LS Mean Dif
Slide 9: Caregivers were Notably Better
9 worsening Because Participants Improved in Hallucinations, Delusions & Anxiety, Caregivers were Notably Better New tool created to measure caregiver burden in DLB -2 -1.5 -1 -0.5 0 0.5 1 1.5 2 2.5 3 0 NPI (Distress) ITT CT1812 Pooled Placebo Baseline Day 28 Day 98 Day 182 114% slowing NPI Distress
Slide 10: Up to 91% Slowing of Cognitive Decline Across Assessments
10 Up to 91% Slowing of Cognitive Decline Across Assessments CT1812 improved patients’ attentiveness and problem solving -1 -0.8 -0.6 -0.4 -0.2 0 0.2 0 MoCA (ITT) Baseline Day 28 Day 98 Day 182 -1 -0.5 0 0.5 1 1.5 0 CAF (fluctuations) (ITT) Baseline Day 28 Day 98 Day 182 -15 -10 -5 0 5 0 CDR - Episo
Slide 11: 52% Preservation in Activities of Daily Living Measures
11 Components of ADL Score 52% preservation in activities of daily living (ADL) measures People on CT1812 Maintained Self-care -10 -8 -6 -4 -2 0 2 0 ADCS-ADL (ITT) CT1812 Pooled Placebo Baseline Day 28 Day 98 Day 182 52% slowing worsening • Bathing • Dressing • Grooming • Feeding • Toileting • Conve
Slide 12: 62% Preservation in Measures of Movement
12 Components of UPDRS: 62% preservation in measures of movement People Treated with CT1812 Maintained Motor Function -2 -1 0 1 2 3 4 5 6 0 MDS-UPDRS Part III (ITT) CT1812 Pooled Placebo Baseline Day 28 Day 98 Day 182 62% slowing worsening • Balance • Speech • Rigidity • Tremor • Gait • Timed up and
Slide 13: Behavior, Cognition, Movement, Function all Improved with CT1812
13 Behavior, Cognition, Movement, Function all Improved with CT1812 Oral once-daily therapy has potential to change the course of disease for patients and families -1 -0.5 0 0.5 1 1.5 0 CAF (fluctuations) Baseline Day 28 Day 98 Day 182 -1 -0.8 -0.6 -0.4 -0.2 0 0.2 0 MoCA Baseline Day 28 Day 98 Day 1
Slide 14: Study Conduct, Disposition and Safety
Anthony O Caggiano, MD, PhD Study Conduct, Disposition and Safety
Slide 15: Study Conduct
15 • Limited physician and site knowledge, experience in DLB • Supported by $30M grant from NIA - R01AG071643 • Conducted at 34 sites in the United States - 14 - LBDA Centers of Excellence - 7 - Academic - 13 - Industry sites • First patient in (FPI): March 2022 (slow start emerging from covid) • La
Slide 16: Participant Disposition
16 Participant Disposition Analysis populations • ITT : 44 • Safety : 43 293 Screened 130 Randomized 44 Randomized to 100mg CT1812 44 Randomized to 300mg CT1812 42 Randomized to placebo Analysis populations • ITT: 44 • Safety: 44 Analysis populations • ITT : 42 • Safety : 42 33 Completed study 11 Di
Slide 17: Patient Characteristics Consistent with Typical DLB Population
17 Pooled CT1812 (n=88) Placebo (n=42) Total (n=130) Age – years* 72.3 (6.89) 73.7 (6.25) 72.8 (6.69) Gender: % Male 83.0 78.6 81.5 Race: % White 92.0 90.5 91.5 Non-Hispanic or Latino % 98.9 92.9 96.9 MMSE* 24.1 (2.65) 23.8 (2.69) 24.0 (2.66) MoCA* 18.7 (4.96) 17.9 (4.62) 18.4 (4.85) CAF* 5.3 (3.62)
Slide 18: COG1201 (SHIMMER): Safety Summary
18 Favorable safety and tolerability profile COG1201 (SHIMMER): Safety Summary The SAE that was related to IP was for subject 125-0003 (CT1812 300mg). The Preferred Term was ‘Metabolic encephalopathy’. Severity was moderate, drug was interrupted, it was rated as “probably related”, and the outcome w
Slide 19: Most Common Treatment-Emergent Adverse Events (TEAEs)
19 Most Common Treatment-Emergent Adverse Events (TEAEs) Nature and severity of adverse event (AE) profile is similar to prior CT1812 trials TEAEs by Preferred Term occurring in 5% of the total safety population, or those in at least 10% of CT1812 treated participants and at least twice the rate of
Slide 20: Summary of SHIMMER Safety and Tolerability Findings
20 • Total AE frequency was similar in CT1812 and placebo • Most AEs were mild or moderate • Fewer Serious AE occurred in the CT1812 treated group compared to placebo treated • There were no deaths related to study drug • Study Discontinuations due to AEs not related to LFTs: - Placebo – 4.8% - 100m
Slide 21: Planning a Path Forward in Neurological Disease
21 Planning a Path Forward in Neurological Disease • Podium presentation at ILBDC – January 2025 • Convene advisors to provide protocol input • Engage with regulatory experts • Conduct commercial research • Prepare for end-of-Phase 2 meetings
Slide 22: SHIMMER Met and Exceeded Objectives and Expectations
22 • COG1201 SHIMMER was a phase 2a safety and tolerability study seeking signals of efficacy in people with dementia with Lewy bodies • The safety and tolerability profile was similar to past experience with CT182 • Clear signals of efficacy were observed - Across Behavioral, Cognitive, Functional
Slide 23: Acknowledgements
23 • Most importantly – each study participant and their care partners • University of Miami and Dr. James Galvin • NIH and NIA for providing funding • Site investigators and personnel • Our collaborators with the Lewy Body Dementia Association • Cognition colleagues and our CRO partners Cognition T
Slide 24: SHIMMER Met and Exceeded Objectives and Expectations
24 • COG1201 SHIMMER was a phase 2a safety and tolerability study seeking signals of efficacy in people with dementia with Lewy bodies • The safety and tolerability profile was similar to past experience with CT182 • Clear signals of efficacy were observed - Across Behavioral, Cognitive, Functional