neflamapimod (VX-745) / CervoMed - LARVOL DELTA

Involvement of p38 MAP Kinase in DLB Pathology and Neflamapimod Development (ADPD 2026) - "Supported by CervoMed, Inc."

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

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

New PK/PD analyses of Phase 2b clinical data (GlobeNewswire) - "Whether receiving DP Batch A or DP Batch, the estimated threshold for therapeutic activity was a trough plasma drug concentration (Ctrough) of 4 ng/mL. This threshold is consistent with prior published clinical data with neflamapimod; In the RewinD-LB trial, there was a notable difference between DP Batch A (50%) and DP Batch B (75%) with respect to the number of participants reaching the threshold Ctrough target of 4 ng/mL (p=0.02 for DP Batch B having a higher percentage achieving the Ctrough target). Consistent with the conclusion that this difference was the primary driver for DP Batch A showing lower clinical activity, the patients in the DP Batch A treatment group who achieved a Ctrough ≥ 4 ng/mL showed a clinical effect, as measured by a change in CDR-SB, that was similar to that seen with DP Batch B."

P2b data • PK/PD data • Dementia • Lewy Body Disease

New analyses of data from RewinD-LB Trial stratified by plasma pTau181 subset demonstrate greater treatment effect with reduced likelihood of AD co-pathology (GlobeNewswire) - "In the initial phase, the participants did not achieve expected plasma drug concentration levels with the neflamapimod capsules used (DP Batch A) and did not demonstrate a statistically significant improvement on the trial’s primary endpoint...In the extension phase, administration of a new batch of capsules (DP Batch B) was associated with expected plasma drug concentration levels and DP Batch B compared to DP Batch A treatment within the extension phase demonstrated a statistically significant and clinically meaningful slowing of clinical progression. Importantly, though, treatment in extension phase capsule batch identity (DP Batch A vs. DP Batch B) remained blinded to participants and site personnel."

P2b data • Dementia • Lewy Body Disease

Fourth Quarter 2025 and Recent Program Highlights (GlobeNewswire) - "CervoMed obtained alignment with the FDA on a proposed Phase 3 trial design to support a potential New Drug Application for neflamapimod in DLB in November 2025 and with other global regulators during the first quarter of 2026. 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, subject to available funding."

New P3 trial • Dementia • Lewy Body Disease

ALS: CervoMed expects initiation of the EXPERTS-ALS trial evaluating neflamapimod in patients with ALS by the end of 2026. (GlobeNewswire)

New trial • Amyotrophic Lateral Sclerosis

CervoMed Announces Presentations at Upcoming AD/PD 2026 Scientific Conference (GlobeNewswire) - "In the Phase 2b RewinD-LB trial, neflamapimod demonstrated a statistically significant and clinically meaningful slowing of clinical progression in patients with dementia with Lewy bodies (DLB) who did not have Alzheimer’s disease (AD) co-pathology during the trial’s extension phase. The secondary analyses of data from the trial to be presented at AD/PD 2026 will include new outcomes by pre-specified plasma pTau181 levels that further support the cutoff to be utilized in the Company’s planned Phase 3 trial in DLB patients to enrich for those without AD co-pathology...The symposium...will highlight scientific, mechanistic, pharmacologic, and clinical data supporting the inhibition of p38 map kinase as a potential promising treatment for DLB."

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

Preliminary Evidence that Neflamapimod has a Beneficial Effect on Basal Forebrain Atrophy Assessed by MRI in Dementia with Lewy Bodies (AAN 2026) - "These findings provide preliminary evidence that neflamapimod may reduce basal forebrain atrophy in DLB and support MRI as a tool to assess treatment effects on cholinergic degeneration."

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

CervoMed Announces Selection of Formulation and Dosing Regimen for Planned Phase 3 Trial in Patients with Dementia with Lewy Bodies (Yahoo Finance) - "To ensure that plasma drug concentrations associated with therapeutic activity are achieved, dosing regimen in the planned Phase 3 trial in dementia with Lewy bodies will be 50mg TID of the stable, crystal form of neflamapimod...CervoMed Inc...announced that it has successfully completed a Phase 1 healthy volunteer study designed to evaluate the pharmacokinetics (PK) of drug product (DP) containing only a new, stable crystal form of neflamapimod and related updates regarding its planned Phase 3 trial in dementia with Lewy bodies (DLB)....The Company plans to initiate a global, pivotal Phase 3 trial in patients with DLB, enriched for those without AD co-pathology, in the second half of 2026, subject to available funding."

New P3 trial • Trial completion • Dementia • Lewy Body Disease

CervoMed’s neflamapimod elected for inclusion in UK EXPERTS-ALS platform designed to prioritize promising treatments for Amyotrophic Lateral Sclerosis (Yahoo Finance) - "UK-based trial first to evaluate neflamapimod in ALS; first person with ALS expected to be dosed by end of 2026...EXPERTS-ALS assesses potential therapies through a randomized, multicenter, open-label, multi-arm trial that evaluates investigational medicines through the measurement of the blood biomarker neurofilament light chain (NfL)...Neflamapimod will be initially evaluated in approximately 35 participants with ALS for 18-24 weeks to determine its impact on NfL levels, with the potential for further evaluation in up to a total of 80 patients."

New trial • Amyotrophic Lateral Sclerosis

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