Slide 1: The Opportunity in Dementia with Lewy Bodies (DLB) for Neflamapimod
Medicines for the Brain The Opportunity in Dementia with Lewy Bodies (DLB) for Neflamapimod June 2025 1 NASDAQ: CRVO
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation includes express and implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, regarding the intentions, plans, beliefs, expectations or forecasts for the future of the Company, including, b
Slide 3: What is the average time from diagnosis of DLB to requiring nursing home care?
A. 2 years What is the average B. 4 years time from diagnosis of DLB to requiring C. 6 years nursing home care? D. 8 years 3 Rongve et al, Int J Geriatric Psychiatry, 2014
Slide 4: Dementia with Lewy Bodies (DLB) is a High-Value, Untapped Opportunity
Dementia with Lewy Bodies (DLB) is a High-Value, Untapped Opportunity DLB represents a large, accessible patient population with no approved treatments to date Ongoing research has provided clear insights on the molecular mechanisms of DLB, paving the way for the first effective treatments DLB is a
Slide 5: New Insights Underscore Potential to Develop Disease-Modifying Medicines for DLB
New Insights Underscore Potential to Develop Disease-Modifying Medicines for DLB DLB is a Distinct Dementia • DLB associated with abnormal deposits (“Lewy bodies”) within neurons of a protein called alpha-synuclein in the brain. Nucleus • About 50% of DLB patients have “pure” DLB Lewy body • Absence
Slide 6: Plasma Levels of Phosphorylated Tau Can Identify and Exclude Patients with AD Co-Pathology
Plasma Levels of Phosphorylated Tau Can Identify and Exclude Patients with AD Co-Pathology in Clinical Trials Amyloid PET Scan Tau PET Scan 6 Diaz-Galvan et al, Alzheimer’s & Dementia, 2023
Slide 7: DLB Without Alzheimer's Disease Related Co-Pathology is a Rare and Valuable Commercial Opportunity
DLB Without Alzheimer’s Disease Related Co-Pathology is a Rare and Valuable Commercial Opportunity Multi-Billion Dollar US Market Opportunity Treatment Landscape • Acetylcholinesterase inhibitors are the 700K mainstay of treatment All Patients • Provide transient improvement in cognition, but no imp
Slide 8: Neflamapimod: Targeting Neuroinflammation Driven Synaptic Dysfunction
Neflamapimod: Targeting Neuroinflammation Driven Synaptic Dysfunction • Oral small molecule inhibitor of alpha isoform of p38 MAP kinase (p38α kinase) • Potent (<10nM IC50), highly selective • Blood-brain-barrier penetrant with brain:plasma ratio of ~2 • Safety profile well defined • Chronic, repeat
Slide 9: Scientific Rationale for Targeting P38α for DLB
Scientific Rationale for Targeting P38α for DLB • P38α is a highly validated target for neurodegeneration, with major roles in1,2: • Neuroinflammatory response3,4 • Tau hyper-phosphorylation5,6 • Axonal transport impairment7 BASAL FOREBRAIN p38α • DLB specific rationale, with P38α CHOLINERGIC NEURON
Slide 10: Preclinical and Clinical Results Prior to Phase 2b Clinical Trial
Preclinical and Clinical Results Prior to Phase 2b Clinical Trial Preclinical Disease processes in basal forebrain reversed Cholinergic neurons in basal forebrain When administered in mice that develop basal forebrain cholinergic degeneration, neflamapimod: Reduced Rab5 activity and tau phosphoryl
Slide 11: RewinD-LB Phase 2b Study in DLB: Design and Conduct
RewinD-LB Phase 2b Study in DLB: Design and Conduct PATIENTS PLACEBO-CONTROLLED EXTENSION PHASE • 159 patients with PHASE OF STUDY (32 weeks) dementia with Lewy (16 weeks) RANDOMIZATION bodies by consensus SCREENING Placebo TID Neflamapimod 40mg TID (Old Capsules) clinical criteria • CDR global scor
Slide 12: In Phase 2b, Clear Benefit Seen Across Primary Endpoint and Multiple Other Clinical Endpoints
In Phase 2b, Clear Benefit Seen Across Primary Endpoint and Multiple Other Clinical Endpoints During Extension Phase CDR-SB Other Endpoints ADCS CGIC • Global measure of • Clinical global impression of • In Phase 2b, cognition that is commonly neflamapimod also change is complementary used as a prim
Slide 13: Relevant CDR-SB Domain Scores in Early-Stage DLB
Relevant CDR-SB Domain Scores in Early-Stage DLB Construct of CDR-SB is such that ≥ 0.5 Change is Inherently Clinically Meaningful Score Judgement & Reasoning Community Affairs Home and Hobbies Personal Care Solves everyday problems & Independent function at usual level 0.0 handles business & financ
Slide 14: Significant Impact on Clinical Worsening in CDR-SB In DLB Patients Without AD Co-Pathology
Significant Impact on Clinical Worsening in CDR-SB In DLB Patients Without AD Co-Pathology (ptau181 < 2.2 pg/mL) Mean Increase (Worsening) in CDR-SB Proportion with Progression (≥ 1.5-point increase in CDR-SB) 60.0% Old Capsules New Capsules ** 1.5 50.0% 45.8% * 1.3 62% relative 40.0% 1.1 67% Reduct
Slide 15: ADCS-CGIC Within-participant Comparison in Participants Who Received Placebo in Initial Phase
ADCS-CGIC Within-participant Comparison in Participants Who Received Placebo in Initial Phase Also Demonstrates Clinical Significance Participants who received placebo and then Participants who received placebo and then New Old Capsules (N=37) Capsules (N=34) 4.8 4.8 4.6 4.6 p = 0.041 4.4 4.4 4.2 4.
Slide 16: Phase 2b Safety and Tolerability Summary
Phase 2b Safety and Tolerability Summary Neflamapimod was well- Adverse events were typically ~90% of patients who mild, and similar to placebo, tolerated, with <4% rate of entered the Extension with the exception of falls which discontinuation due to Phase continued through to were significantly lo
Slide 17: Incidence of Falls Significantly Reduced in Participants with DLB without AD Co-Pathology
Incidence of Falls Significantly Reduced in Participants with DLB without AD Co-Pathology (Screening Plasma ptau181 < 2.2 pg/mL) Double-Blind Placebo-Controlled Phase Extension Phase Through to Week 16 25 p=0.007 p=0.025 20 19.7% Incidence of Falls 15 15.4% 10 12.1% 5 4.0%** 0 Placebo (N=71) NFMD (O
Slide 18: Phase 2b Neflamapimod Summary
Phase 2b Neflamapimod Summary Clinical Dementia Rating Sum of Boxes (CDR-SB, Total Score = 0-18) Neflamapimod has demonstrated proof-of-concept in DLB Data across clinical endpoints demonstrates that neflamapimod slows the clinical progression of DLB Cervomed will meet with global regulators to reac
Slide 19: Projected Phase 3 Trial Design for Neflamapimod
Projected Phase 3 Trial Design for Neflamapimod PLACEBO-CONTROLLED STUDY KEY PARAMETERS (24 weeks) • DLB by consensus RANDOMIZATION criteria and no AD SCREENING Placebo co-pathology by plasma phospho-tau Neflamapimod • Primary Endpoint: Enrollment Week 24 CDR-SB • Approximately 300 patients >40 site
Slide 20: Neflamapimod is a Substantially Derisked Asset Targeting an Untapped Multi-Billion Dollar Opportunity
Neflamapimod is a Substantially Derisked Asset Targeting an Untapped Multi-Billion Dollar Opportunity Clinical Dementia Rating Sum of Boxes (CDR-SB, Total Score = 0-18) DLB clinical progression is rapid; significant clinical effect observable in short-term studies Phase 2b Positions Neflamapimod for