Slide 1: Efficacy and safety results of the RewinD-LB phase 2b clinical trial of neflamapimod in DLB
§ CERVOMED Medicines for the Brain Efficacy and safety results of the RewinD-LB phase 2b clinical trial of neflamapimod in dementia with Lewy bodies (DLB) LS Honig?, SN Gomperts?, JP Taylor?, ND Prins*, A Gardner, K Blackburn’, JJ Alam, JE Galvin’ 1. Columbia University Irving Medical Center — New Y
Slide 2: Forward-Looking Statements
Forward-Looking Statements This proxetaton indus oxpres ord imped forwardloking statements ihn the meaning of th Privo Sects igen Rofom Act af 1995, ot omendh regerlng the Inienitons, plans, belo, expectatiens or frees for he fle of CorvoMed In (he “Company”, nding, bu no imtoo: he terepestie pool o
Slide 3: Disclosures
Disclosures ¢ Neflamapimod is an investigational drug e J. Alam, A. Gardner, and K. Blackburn are employees of CervoMed Inc, the company developing neflamapimod ¢ §.N. Gomperts and J-P Taylor each have acted as a consultant for CervoMed
Slide 4: Neflamapimod: Oral small molecule p38 Kinase Inhibitor that Targets Cholinergic Dysfunction and Degeneration
Neflamapimod: Oral small molecule p38. Kinase Inhibitor that Targets Cholinerg' Dysfunction and Degeneration B-CTF of APP! Nevroinflammation, a- | synuclein, AB Trovs ) (UME pst. a Say Neflamapimod ‘Synaptic Dysfunction, Tau Hyperphosphorylation, Defects in Axonal Transport and Nerve Growth Factor S
Slide 5: Neflamapimod Background
Neflamapimod Background Pre-Clii Through inhibiting p38. acts en molecular ical mechanisms underlying cholinergic degeneration = Ras: = Tew In mice that develop basal forebrain cholinergic degeneration YL RabS activity and | tov phosphorylation Reverses loss of cholinergic (ChaT +) neurons inthe bas
Slide 6: Phase 2a AscenD-LB Results Stratified by Plasma ptau181 Levels
Phase 2a AscenD-LB Results Stra’ ied by Plasma ptau181 Levels ‘Treatment Effect of 40mg TID Neflamapimod vs. Placebo ‘A. Clinical dementia rating sumoboxes(CORS8) _B. Timed upandgo (TUG) 19. (versllstay Population (h-85 pth oncrestnan fic daa) 2 sie #8 3S oo. ewenne sora ole 5 Miyed ge Seno a ecm ne
Slide 7: RewinD-LB Phase 2b Clinical Trial
RewinD-LB Phase 2b Clinical Trial Rewin))-LB :_| | rey oO oO ° INTERVENTION, EEG: bela functional connectivity (primary), eyes-clored to eyer-open alpha reactivity ‘or maeng placebo capo, TID for 16 wos followed by 32k opemtabel Paina biomarker: GFAP ot week 16 ‘netlamepinod tectment extension
Slide 8: RewinD-LB Investigator Sites
RewinD-LB Investigator Sites USA A. Burke, Barrow Neurological institute, Phoenix AZ . Sprecher, Banner Sun Health Research Institute, Sun City AZ K- Bradley, Banner Alhelmer's Institute, Tucson AZ Hess, UCSD, La Jala, CA A.Riter, Hoag Memorial Hospital Presbyterian, Newport Beach CA ‘MAL Purino, $C
Slide 9: Consort Participant Flow Diagram — Double-Blind Phase
Consort Participant Flow Diagram — Double-Blind Phase 335 evaluated for eligibility 176 excluded | 182 for not meeting ptau181 criteria + 29{f0r not meeting global COR criteria +12 for not meeting probable DLB diagnosis = 2 other | ] [8 atanapinoa '5 Early Discontinuations 3 for adverse events, 2 wi
Slide 10: Baseline Characteristics
Baseline Characteristics Placebo Neflamapimod All (n=8o) (N=79) (v=159) ‘Age 70.7 (5.84) 72.16.35) 71.46.12) Male 67 (63.8%) 69(873%) 136 (85.5%) MIMSE (ne78 nro) 23.34.57) 23.6 (4.25) 235(4.41) CDR-SB = 79980) 423(171) 445 (217) 434(195) IsLT Immediate 13.9(5.32) 13,7(497) 13.8 (5.13) Core Clinical
Slide 11: Primary Endpoint Results
Primary Endpoint Results 56 52 48 36 32 Mean (s.e.m.) Clinical Dementia Rating Sum of Boxes (CDR-SB) Score by Study Visi Placebo (N=79, 19, 78,77,77)_ —-Neflamapimod (N=79, 19, 77, 74,74) sete Week Week ‘Week? Weeks Primary Statistical Analysis: Change from Baseline* Placebo NEMD (n=79) (n=79) NEMD
Slide 12: Secondary (TUG, NTB) and Tertiary (NPI-10) Endpoint Results
Secondary (TUG, NTB) and Tertiary (NPI-10) Endpoint Results Seconds Mean {s.¢.m,) Change from Baseline in. ‘Mean (s.e.m.) Change from Baseline in ‘Mean (SEM) Change from Baseline ‘Timed Up and Go (TUG) Test Neuropsychological Test Battery (NTB) ‘In 10-Atem Neuropsychiatric Inventory (NPI-10) | ie bi
Slide 13: CGIC Results (Secondary Endpoint)
CGIC Results (Secondary Endpoint) Number of Participants in Each Category at Week 16 1 Placebo (N=78) 3 | | - ey om! _ i i | _! Markedinprowoment —Medeste—Minimalimprovenent_ orange Rimimslerrenng. Madate Werarrg. Mat Weezaing mprovemant 2
Slide 14: Safety
Safety ° Generally well-tolerated, with no new safety signals * One early discontinuation for adverse events in placebo group (death due to unknown cause ) and three with neflamapimod treatment (pleural effusion, LFT abnormal*, UTI worsening) * 8 SAEs in placebo and 5 with neflamapimod treatment. Al
Slide 15: Most Common Treatment Emergent Adverse Events
10 Most Common Treatment Emergent Adverse Events PLACEBO NeMD ALL (280) (we79) (v=159) falls 15(18.8%) 25.2% 27 (17%) covin.19 38.8%) 8 (101%) 11(6.9%) Diarrhea 38.8%) 67.6%) 95.7%) Headache 10 (12.5%) 516.3%) 15 (9.4%) Fatigue 607.5%) 516.3%) 11(6.9%) Urinary Tract Infection 607.5%) 516.3%) 11(6.9%
Slide 16: Plasma Drug Concentration Measurements
Plasma Drug Concentration Measurements + In RewinD-LB, trough plasma drug concentrations (Crroug:) obtained at week 2 of the double-blind phase of the study and week 4 of the oper-label extension (OLE) — Participant asked to not take morning dose and have blood sample for plasma drug concentration o
Slide 17: Plasma Drug Concentrations
Plasma Drug Concentrations + Mean Crougn (3.9 ng/mL, SD=1.5) in RewinD-LB was similar to that seen with 40mg BID, both in AD and in AscenD-LB, i.e., target plasma drug concentration was lower than targeted. 16
Slide 18: Plasma Drug Concentrations
Plasma Drug Concentrations + Mean Cieugh (3.9 ng/mL, SD=1.5) in RewinD-LB was similar to that seen with 40mg BID, both in AD and in AscenD-LB, i.e., target plasma drug concentration was lower than targeted » Evaluation of the capsules utilized in the double-blind phase of the trial is ongoing: — No
Slide 19: Plasma Drug Concentrations
Plasma Drug Concentrations + Mean Cieugh (3.9 ng/mL, SD=1.5) in RewinD-LB was similar to that seen with 40mg BID, both in AD and in AscenD-LB, i.e., target plasma drug concentration was lower than targeted + Evaluation of the capsules utilized in the double-blind phase of the trial is ongoing — No e
Slide 20: Upcoming Week16 OLE Analysis
Upcoming Week16 OLE Analysis Rewin)-LB NaN STUDY. Open tebe Exterten 18) = (beets) twee) #1 | 2) Noflamapimod 40m TD (Old Capsies) ‘aflame vod 40mg (New Copsve) Wook 18 OLE Wek 16 leak a ° O- o——}-o0 + OLE Anetyss March 2025) PARTICIPANTS AND INTERVENTION DURING OLE (OUTCOME MEASURES + Old capsules
Slide 21: Summary and Next Steps
Summary and Next Steps * No discernible differences between neflamapimod 40mg TID and placebo treatment groups during the double-blind phase of the clinical study * Measured trough plasma drug concentrations during the double-blind phase are similar to those seen with a lower dose of 40mg BID in ear
Slide 22: Acknowledgements
Acknowledgements * Patients, caregivers, study investigators and clinical site staff involved with both the AscenD-LB and RewinD-LB studies * Clinical project teams at Worldwide Clinical Trials and CervoMed, Inc. + Members of the Data Safety Monitoring Board (DSMB) for the RewinD- LB study: Kenneth