Slide 1: LB31 - Results of the Phase 2b Trial of Neflamapimod in Dementia with Lewy Bodies
LB31 - Results of the Phase 2b Trial of Neflamapimod in Dementia with Lewy Bodies John-Paul Taylor1, Stephen N Gomperts2, Lawrence S Honig3, Niels D Prins4, Amanda Gardner5, Kelly Blackburn5, John Alam5, James E Galvin6 1Newcastle University - Newcastle Upon Tyne (United Kingdom), 2Massachusetts Gen
Slide 2: Disclosures
Disclosures • Neflamapimod is an investigational drug • J. Alam, A. Gardner, and K. Blackburn are employees of CervoMed Inc, the company developing neflamapimod • S.N. Gomperts and J-P Taylor each have acted as a consultant for CervoMed Inc • The other co-authors have no disclosures to declare 2
Slide 3: RewinD-LB Investigator Sites
RewinD-LB Investigator Sites USA USA, continued A. Burke, Barrow Neurological Institute, Phoenix AZ A. Bozoki, U. of North Carolina, Chapel Hill NC D. Shprecher, Banner Sun Health Research Institute, Sun City AZ R. Drake, Neuroscience Research Center, Canton OH K. Bradley, Banner Alzheimer’s Institu
Slide 4: Dementia with Lewy Bodies (DLB): Background
Dementia with Lewy Bodies (DLB): Background • High unmet need • Significant impact on quality of life and caregiver burden • Progresses more rapidly than AD, with average time from diagnosis to requiring nursing home care being 2 years • Progressive α-synucleinopathy characterised by widespread cort
Slide 5: Neflamapimod is An Oral p38α Kinase Inhibitor That Targets Dysfunction and Degeneration of Acetylcholine-Producing Neurons
Neflamapimod is An Oral p38α Kinase Inhibitor That Targets Dysfunction and Degeneration of Acetylcholine-Producing Neurons α-synuclein build-up Increased tau and toxicity13,14 hyperphosphorylation5,6 Reduced tau acetylcholine Release11,12 Impaired retrograde axonal transport7,12 Basal Forebrain (hyp
Slide 6: Positive Preclinical and Phase 2a (AscenD-LB) Data Validate Drug Target and Support Advancement to Phase 2b
Positive Preclinical and Phase 2a (AscenD-LB) Data Validate Drug Target and Support Advancement to Phase 2b Preclinical Disease processes in basal forebrain reversed Cholinergic Neurons in Basal Forebrain Healthy Diseased Diseased Mice Mice Mice Treated NFLM When administered in mice that develop ba
Slide 7: RewinD-LB Phase 2b Study in DLB: A Two-Part Study Design
RewinD-LB Phase 2b Study in DLB: A Two-Part Study Design PATIENTS Part A Part B • 159 patients with dementia with Lewy bodies by consensus PLACEBO-CONTROLLED OPEN LABEL EXTENSION PHASE clinical criteria PHASE OF STUDY (32 weeks) (16 weeks) • CDR global score of RANDOMIZATION 0.5 or 1.0 at baseline S
Slide 8: Plasma pTau181 Levels Were Used to Enrich Study Enrollment for Patients without AD Co-Pathology
Plasma pTau181 Levels Were Used to Enrich Study Enrollment for Patients without AD Co-Pathology Inclusion At the time RewinD-LB was initiated (mid-2023), and based on a limited data set, criteria in 27.2 pg/ml was estimated to be the optimal cutoff RewinD-LB was for AD co-pathology in patients with
Slide 9: Baseline Characteristics: Similar Across Study Phases, Patient Subsets, and Drug Batches
Baseline Characteristics: Similar Across Study Phases, Patient Subsets, and Drug Batches Randomized Phase Extension Phase Extension Phase (All Participants) (<21 pg/mL subset) NFMD Placebo DP Batch A DP Batch B DP Batch A DP Batch B (DP Batch A) Number of Participants 79 80 55 94 38 55 Age 70.7 (5.8
Slide 10: RewinD-LB Phase 2b Study in DLB: A Two-Part Study Design
RewinD-LB Phase 2b Study in DLB: A Two-Part Study Design PATIENTS Part A Part B • 159 patients with dementia with Lewy bodies by consensus PLACEBO-CONTROLLED OPEN LABEL EXTENSION PHASE clinical criteria PHASE OF STUDY (32 weeks) (16 weeks) • CDR global score of RANDOMIZATION 0.5 or 1.0 at baseline S
Slide 11: No Significant Differences between Placebo and Neflamapimod in Primary Outcome Measures During Placebo-Controlled Phase
No Significant Differences between Placebo and Neflamapimod in Primary Outcome Measures Were Observed During Placebo-Controlled Phase of Study PATIENTS • 159 patients with Part A dementia with Lewy bodies by consensus clinical criteria • CDR global score of Change in CDR-SB from baseline 0.5 or 1.0
Slide 12: RewinD-LB Phase 2b Study in DLB: A Two-Part Study Design
RewinD-LB Phase 2b Study in DLB: A Two-Part Study Design PATIENTS Part A Part B • 159 patients with dementia with Lewy bodies by consensus PLACEBO-CONTROLLED OPEN LABEL EXTENSION PHASE clinical criteria PHASE OF STUDY (32 weeks) (16 weeks) • CDR global score of RANDOMIZATION 0.5 or 1.0 at baseline S
Slide 13: Mean Plasma Drug Trough Concentration Was Significantly Higher with DP Batch B than DP Batch A
Mean Plasma Drug Trough Concentration Was Significantly Higher with DP Batch B than in DP Batch A Ctrough Levels with DP Batch A in Placebo-Controlled Phase and DP Batch B in Extension Phase • Mean plasma drug trough concentration (Ctrough) of DP Batch A was below expected 5.0 ng/ml and similar to t
Slide 14: Introduction of New Batch of Neflamapimod (DP Batch B) Achieved Target Drug Concentrations
Introduction of New Batch of Neflamapimod (DP Batch B) Achieved Target Drug Concentrations and Enabled Robust Extension-Phase Analyses Number of NEFLAMAPIMOD ONLY EXTENSION PHASE1 (32 weeks) Neflamapimod Dosing Groups Participants and Comparisons at Start of Extension • DP Batch A: Did not achieve e
Slide 15: Significant Effect on Primary Outcome Measure (CDR-SB) Over 16 Weeks When Target Plasma Concentrations Achieved
Significant Effect on Primary Outcome Measure (CDR-SB) Over 16 Weeks When Target Plasma Concentrations Achieved with DP Batch B Neflamapimod Dosing Groups and Comparisons DP Batch A P=0.007 DP Batch B vs. DP Batch A p=0.024 DP Batch B vs. DP Batch A • DP Batch A: Did not achieve expected and targete
Slide 16: Within-Subject Analysis of Change in CDR-SB Confirms Significant Clinical Effect
Within-Subject Analysis of Change in CDR-SB Confirms Significant Clinical Effect; Most Prominently in Patients with Low Likelihood of AD Co-Pathology Change in CDR-SB in During Either Randomized Phase or 16 Weeks of Extension Phase ≥21 pg/mL pTau 181 <21 pg/mL pTau181 Placebo/DP Batch A (N=11) Place
Slide 17: Clinical Effect Observed by CDR-SB Is Durable Out to 32 Weeks of Treatment
Clinical Effect Observed by CDR-SB Is Durable Out to 32 Weeks of Treatment Participants with Screening Plasma All Participants (mITT) pTau181 < 21 pg/mL 2.5 2.5 p=0.021 DP Batch B vs DP Batch A p=0.032 DP Batch B vs DP Batch A Change in CDR-SB from Baseline Change in CDR-SB from Baseline 2 2 to Week
Slide 18: Risk of Clinical Progression Reduced and Time to Progression Increased with Neflamapimod
Risk of Clinical Progression (≥ 1.5 Pt Increase in CDR-SB) Reduced and Time to Progression Increased with Neflamapimod in Patients Participants with Screening Plasma pTau181 < 21 pg/mL DP Batch B DP Batch A Placebo Risk of Progression Hazard Ratio % (95% confidence Reduction P-value interval) in Ris
Slide 19: Positive Effects on ADCS-CGIC Achieved and Corroborate CDR-SB Results
Positive Effects on ADCS-CGIC Achieved and Corroborate CDR-SB Results Target Concentration Not Achieved Target Concentration Achieved Mean ADCS-CGIC Score All 4.11 Participants Mean ADCS-CGIC Score Participants with Low Likelihood of AD Pathology (Screening 3.82 Difference = -0.82 plasma pTau181 <21
Slide 20: Treatment Effect Across Multiple Secondary and Exploratory Clinical Endpoints Favor Treatment with DP Batch B
Treatment Effect Across Multiple Domain Specific Secondary and Exploratory Clinical Endpoints Favor Treatment with DP Batch B Mean Difference (95% Confidence Interval) Between DP Batch A and DP Batch B in Change from Baseline to Week 16 of Extension All Patients < 21 pg/mL ptau181 Subset Timed Up an
Slide 21: Neflamapimod Achieves Significant Reduction in Key Biomarker of Neurodegeneration
Neflamapimod Achieves Significant Reduction in Key Biomarker of Poster Neurodegeneration 071 Within Participant Comparison (N=48) of Effect on Plasma GFAP: DP Batch B vs. Placebo p=0.016 DP Batch B vs P=0.007 DP Batch B vs. DP Batch A Placebo (Randomized Phase) (change from start of extension to Wee
Slide 22: Neflamapimod Exhibited a Favorable Safety Profile
Neflamapimod Exhibited a Favorable Safety Profile Neflamapimod Was Well-tolerated with No New Safety Signals Identified All events of liver enzyme The incidence of Only adverse event elevation were reversible; discontinuation due to seen at greater than none were associated with adverse events was l
Slide 23: Alignment Achieved with FDA on Global Phase 3 Clinical Trial Design and Path to Registration
Alignment Achieved with FDA on Global Phase 3 Clinical Trial Design and Path to Registration KEY PARAMETERS PHASE 3 PLACEBO-CONTROLLED STUDY (32 weeks) • DLB by consensus RANDOMIZATION SCREENING Placebo criteria Neflamapimod • Primary endpoint: Change in CDR-SB Enrollment Week 32 • Approximately 300
Slide 24: Advancing Neflamapimod as A Potential First-in Class Therapy for the Treatment of DLB
Advancing Neflamapimod as A Potential First-in Class Therapy for the Treatment of DLB Durable, clinically “Pure” DLB represents Well documented significant effect and an area of high unmet Alignment achieved with scientific rationale and favorable safety profile of need with no currently FDA on regi
Slide 25: Acknowledgements
Acknowledgements • Patients, caregivers, study investigators, and clinical site staff involved with the RewinD-LB study • Clinical project teams at Worldwide Clinical Trials and CervoMed, Inc. • Members of the Data Safety Monitoring Board (DSMB) for the RewinD-LB study: Kenneth Rockwood MD, FRCPC, F