neflamapimod (VX-745) / CervoMed - LARVOL DELTA

NEFLAMAPIMOD TREATMENT EFFECTS IN PATIENTS WITH DEMENTIA WITH LEWY BODIES WITHOUT CONCOMITANT AD PATHOLOGY IN THE REWIND-LB CLINICAL STUDY (NCT05869669) (ADPD 2026) - P2 | "With achievement of targeted plasma drug concentrations, neflamapimod demonstrates robust clinical activity in patients with DLB without AD pathology."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • p-tau181

A Systematic Review to Evaluate the Effect of Neflamapimod on Cognitive Function and Progression of Dementia. (PubMed, Neurol India) - "The findings of the current review suggested that while the cognitive effects of neflamapimod remain uncertain, its ability to influence disease-specific biomarkers makes it a potential drug to be used in dementia. This review connects biological and clinical outcomes, paving the way for future advancements in dementia treatment strategies."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • Lewy Body Disease • CSF P-tau

Drug Development. (PubMed, Alzheimers Dement) - "These findings enhance understanding of LD formation and isoform-specific differences in astrocytes. Given the role of LDs in AD, these insights may contribute to understanding AD pathogenesis and identifying therapeutic strategies."

Journal • APOE • PLIN2

Developing Topics. (PubMed, Alzheimers Dement) - "The results further demonstrate that neflamapimod beneficially impacts clinical progression in patients with DLB and confirm with larger participant numbers the phase 2a finding that AD co-pathology impacts response to neflamapimod treatment."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Dementia • CSF P-tau • p-tau181

Developing Topics. (PubMed, Alzheimers Dement) - P2 | "With achieving target plasma drug concentrations, there was evidence of neflamapimod having a meaningful impact on clinical progression, as assessed by the CDR-SB and CGIC, in patients with DLB who do not have AD co-pathology. The pattern of the effects across the full set of clinical endpoints evaluated are consistent with preclinical results in which neflamapimod beneficially impacts the disease process in the basal forebrain."

Clinical • Journal • p-tau181

Results of the Phase 2b Trial of Neflamapimod in Dementia with Lewy Bodies (CTAD 2025) - No abstract available

Late-breaking abstract • P2b data • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease

Neflamapimod Significantly Lowers Plasma GFAP and Correlates with Clinical Benefit in Dementia with Lewy Bodies: Results from the RewinD-LB Trial (CTAD 2025) - No abstract available

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • GFAP

Mechanisms of acute pain involve spinal IL17-TNF-α/IL-6–p38 MAPK activation in sickle cell disease (ASH 2025) - "We nextexamined if the novel transdermal curcumin (TDC; Vasceptor, Vascarta Inc.), which reduced inflammationand oxidative stress in sickle mice in the periphery (Goel et al., PNAS nexus 2025), has the potential toinhibit spinal inflammation, oxidative stress, and p38 phosphorylation...Since p38 is activated by cytokines and is also involved in the transcriptional regulation ofcytokines, leading to oxidative stress, we next examined if TDC or inhibition of p38 with neflamapimod(Nef) would prevent hypoxia-induced oxidative stress in a sickle microenvironment in the peripheral andCNS...We conclude that IL-17 orchestrates acute pain bypromoting IL-17-TNF-α/IL-6–p38 cascade in the CNS and periphery, leading to oxidative stress andmitochondrial dysfunction in sensory neurons. TDC interrupts this SCD pathophysiological cascade,suggestive of a preventive effect on acute pain episodes in SCD."

Genetic Disorders • Hematological Disorders • Metabolic Disorders • Musculoskeletal Diseases • Pain • Sickle Cell Disease • IL17A • IL6 • TNFA

CervoMed Announces Late-Breaking Data at the 18th CTAD Conference Demonstrating Neflamapimod Significantly Slows Clinical Progression in Dementia with Lewy Bodies (GlobeNewswire) - "Key analyses of the extension phase of the RewinD-LB trial showed: A significant improvement on the primary endpoint, CDR-SB (Clinical Dementia Rating Sum of Boxes), at week 16 of the extension phase, with a mean change that was 52% lower with DP Batch B compared to DP Batch A in all participants and 82% lower in patients with a screening plasma ptau181 of <21.0 pg/mL (i.e., patients without AD co-pathology). The clinical effect in CDR-SB was durable to 32 weeks, with a 65% reduction in clinical worsening in all participants (mean increase=1.73 with DP Batch A vs. 0.53 with DP Batch B) and an 89% reduction in clinical worsening in the <21.0 pg/mL ptau181 subgroup (mean increase=1.44 with DP Batch A vs. 0.16 with DP Batch B)."

P2b data • Dementia • Lewy Body Disease

CervoMed preparing to initiate Phase 3 registrational trial in patients with DLB in the second half of 2026 (GlobeNewswire)

New P3 trial • Dementia • Lewy Body Disease

CervoMed Presents New Plasma Biomarker Data That Indicates Neflamapimod Broadly Improves Neuroinflammation and Neurodegeneration in Dementia with Lewy Bodies (DLB) (GlobeNewswire) - "During the 32 weeks of the Extension there was a significant reduction in plasma GFAP levels in participants who received DP Batch B (median -16.0, IQR: -35, +6.7; p<0.0001 for change from start to Week 32 of the Extension). Change in plasma GFAP over 32 weeks was significantly lower during treatment with DP Batch B (mean -16.7 pg/mL) compared to change in the same participants during placebo administration (mean +5.8 pg/mL) over 16 weeks (median difference = -23.5 pg/mL, p=0.016, Wilcoxon rank sum test)."

Biomarker • P2b data • Dementia • Lewy Body Disease

Butyrate regulates the blood-brain barrier transport and intra-endothelial accumulation of Alzheimer's disease Amyloid-beta peptides. (PubMed, bioRxiv) - "The roles of various molecular mediators were confirmed using specific inhibitors (MK2206, Trametinib, Rapamycin, VX-745). These changes may also improve the integrity of BBB tight junctions by increasing claudin-5 expression and extracellular matrix, and by upregulating TIMP-2 expression. This study highlights butyrate's potential as a therapeutic modulator of AD-related BBB dysfunction."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42 • CLDN5 • TIMP2

CervoMed to Share New Data on Neflamapimod as a Treatment for Dementia with Lewy Bodies at the 18th Clinical Trials on Alzheimer's Disease (CTAD) Conference (GlobeNewswire) - "In a late-breaking oral session by John-Paul Taylor...and Chief Investigator of the RewinD-LB study for the UK, the full results of the Phase 2b RewinD-LB trial, including new data on the effects of neflamapimod treatment at 32 weeks, will be presented...In addition, a poster presentation will highlight important findings from the RewinD-LB study regarding the utility of, and the treatment effects of neflamapimod on widely used neurodegeneration biomarkers in the trial, including plasma glial fibrillary acidic protein (GFAP), plasma neurofilament light chain (NfL), and beta amyloid 42/40 ratio."

Late-breaking abstract • P2b data • Dementia • Lewy Body Disease

Pharmacological reversal of LPS-induced cognitive impairments: evidence for inflammation-dependent and independent mechanisms (Neuroscience 2025) - "Fifteen compounds proved effective in reversing cognitive deficits and were categorized as follows: i) Anti-inflammatory NSAIDs & Steroids: Ibuprofen, indomethacin, sulindac, dexamethasone...iii) Synaptic & Neurotransmitter Modulators: Memantine, donepezil, GRN 529. iv) Metabolic & Signaling Agents: Metformin, semaglutide, neflamapimod. Two interventions—nilotinib and methylene blue—were ineffective...The convergence of benefits across anti-inflammation, oxidative stress reduction, synaptic modulation, and metabolic regulation underscores the multifactorial nature of inflammation-driven neurodegeneration. Identifying both effective and ineffective agents highlights the model's translational potential and discriminative validity."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease

Targeting p38 Mitogen Activated Protein Kinase to Ameliorate Pain in SCD (ASH 2023) - "Neflamapimod (Nef) is a novel inhibitor of p38 MAPK phosphorylation with significant anti-inflammatory effects, mediated by IL-1β and TNF α...Pain and cognitive impairment co-exist in SCD. Therefore, Nef has the potential to reduce pain and improve cognitive function in SCD."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Depression • Diabetic Neuropathy • Genetic Disorders • Hematological Disorders • Immunology • Neuralgia • Osteoarthritis • Pain • Peripheral Neuropathic Pain • Psychiatry • Rheumatology • Sickle Cell Disease • CASP3 • CRP • IL1B • TNFA

CervoMed Reports Third Quarter 2025 Financial Results and Provides Corporate Updates (CervoMed Press Release) - "Initial biomarker data from Phase 2a trial in a sub-type of frontotemporal dementia (FTD) and topline results from Phase 2a trial in recovery after stroke expected in 2026."

P2a data • Dementia • Ischemic stroke

CervoMed Announces Alignment with FDA on Registration Path for Neflamapimod in Dementia with Lewy Bodies (GlobeNewswire) - "Based on FDA feedback, CervoMed plans to initiate a single, global, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of neflamapimod in approximately 300 patients with DLB by consensus clinical criteria in the second half of 2026. The trial will exclude patients who have historical evidence of Alzheimer’s disease (AD) co-pathology by brain imaging scan or cerebrospinal fluid sampling...Participants will be randomized 1:1 to receive either oral neflamapimod or placebo for 32 weeks, followed by a neflamapimod only extension for 48 weeks....CervoMed expects feedback from other global regulators in the coming months and to announce additional details regarding the planned Phase 3 trial design in early 2026 following these interactions."

FDA event • New P3 trial • Dementia • Lewy Body Disease

CervoMed Inc…announced it has received written feedback from the U.S. Food and Drug Administration (FDA) aligning on key aspects of CervoMed’s proposed Phase 3 clinical trial of neflamapimod…for the treatment of dementia with Lewy bodies (DLB) to support a potential New Drug Application (NDA) submission. (CervoMed Press Release) - "Based on FDA feedback, CervoMed plans to initiate a single, global, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of neflamapimod in approximately 300 patients with DLB by consensus clinical criteria in the second half of 2026....CervoMed expects feedback from other global regulators in the coming months and to announce additional details regarding the planned Phase 3 trial design in early 2026 following these interactions."

Clinical protocol • FDA event • New P3 trial • Dementia • Lewy Body Disease

A Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: EIP Pharma Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease

CervoMed Announces New Data from Phase 2b Trial Demonstrating Neflamapimod's Potential as a Treatment for Dementia with Lewy Bodies (GlobeNewswire) - "Significant improvement relative to placebo on primary outcome measure, change in Clinical Dementia Rating Sum of Boxes (CDR-SB), demonstrated in a within-subject analysis in participants with low likelihood of having Alzheimer’s disease (AD) co-pathology; Significant reduction in plasma levels of a well-established biomarker of neurodegeneration, plasma glial fibrillary acidic protein (GFAP), correlated to treatment response assessed by CDR-SB....On the primary endpoint of change in CDR-SB over 16 weeks, there was a trend toward NFMD/A (Drug product batch that did not achieve targeted plasma drug concentrations, 'old capsules') relative to placebo (difference −0.53, p=0.10, linear mixed-effects model) during the Initial Phase of the trial."

P2b data • Dementia • Lewy Body Disease

CervoMed Highlights Neflamapimod's Potential Benefits in Session on Dementia with Lewy Bodies at the 150th Annual American Neurology Association Conference (GlobeNewswire) - "'Following the positive data showing neflamapimod reduced the risk of clinically significant worsening on the Clinical Dementia Rating Sum of Boxes (CDR-SB) in our Phase 2b trial, including a 74% risk reduction relative to placebo in patients who have a low likelihood of having concomitant AD pathology, we are actively preparing to begin a Phase 3 trial in DLB patients and expect to reach alignment on the design of that trial with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2025.'"

Clinical protocol • New P3 trial • P2b data • Dementia • Lewy Body Disease

A Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: EIP Pharma Inc | Trial completion date: Jan 2026 ➔ Apr 2026 | Trial primary completion date: Dec 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease

RewinD-LB - Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies (clinicaltrials.gov) - P2 | N=159 | Completed | Sponsor: EIP Pharma Inc | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease

CervoMed Announces 32-Week Data from RewinD-LB Trial Extension Phase Showing Neflamapimod’s Sustained Effect on Slowing Clinical Progression in Patients with Dementia with Lewy Bodies and Associated Reduction in a Key Plasma Biomarker of Neurodegeneration (GlobeNewswire) - P2b | N=159 | RewinD-LB (NCT05869669) | Sponsor: EIP Pharma Inc | "'we progress towards initiating a Phase 3 trial and prepare to meet with the U.S. Food and Drug Administration in the fourth quarter of 2025 to align on the trial design.'...Based on the primary endpoint of Clinical Dementia Rating Sum of Boxes (CDR-SB), patients treated with neflamapimod showed 54% risk reduction in clinically significant worsening compared to control at Week 32 of treatment (p=0.0037). This risk reduction improved to 64% (p=0.0001) among patients who have minimal evidence of AD co-pathology (ptau181 < 2.2 pg/mL at screening)....At Week 32 of the Extension phase, there was a statistically significant reduction (p<0.0001) from baseline (i.e., start of extension) in GFAP plasma levels in patients who received New Capsules for all 32 weeks, with a mean change of -18.4±4.0 pg/mL in all participants (N=107)..."

New P3 trial • P2b data • Dementia • Lewy Body Disease

Recent Highlights and Anticipated Milestones (GlobeNewswire) - "Initial safety, biomarker and pharmacokinetic data from an ongoing trial in patients with mild-to-moderate DLB evaluating a twice daily regimen (80mg BID) of neflamapimod are expected to be available in the fourth quarter of 2025."

P2a data • Dementia • Lewy Body Disease