Announcement • Apr 22
CervoMed Inc Announces New Data on Neflamapimod Demonstrating Increased Basal Forebrain Volume and Functional Connectivity in Dementia with Lewy Bodies
CervoMed Inc. presented the first-ever, placebo-controlled magnetic resonance imaging (MRI) analyses providing evidence that neflamapimod may increase the size and enhance the function of the basal forebrain in patients with dementia with Lewy bodies (DLB) at the 2026 AAN Annual Meeting in Chicago. Basal forebrain (BF) atrophy is the primary pathogenic driver of disease expression and progression in DLB. Structural and functional MRI were performed at baseline, week 16, and week 48 in patients enrolled in the RewinD-LB trial in the United Kingdom and the Netherlands (8 neflamapimod treated and 10 placebo recipients during 16-week placebo-controlled period; and 16 neflamapimod recipients, including 11 with fMRI data on active neflamapimod, during the 32-week extension period). Volumes (mm3) of the left and right BF and Nucleus basalis of Meynert (NbM) — the major cholinergic cluster within the BF — and functional connectivity between the BF and NbM to the default mode network (DMN) were quantified. Disruption in BF-DMN connectivity is linked to neurodegenerative disorders where these areas exhibit abnormal activity, such as DLB. All image analyses were conducted on a blinded basis by Amsterdam UMC, utilizing an analytic approach to quantitate BF volume that had been validated against pathology at autopsy. As AD co-pathology would not be expected to impact direct effects on the basal forebrain, the statistical analyses were not stratified by screening plasma pTau181 level. Baseline volumes (mm³) were comparable between groups in the left BF [placebo=315(SD=47), neflamapimod=296(51)], right BF [309(47), 310(47)], left NbM [185(33), 168(21)], and right NbM [269(45), 253(33)]. At week 16, mean change from baseline in right BF volume decreased (–13.3±6 mm3) with placebo and increased with neflamapimod (+10.9 ± 7.3 mm3, p=0.022 vs. placebo). In addition, there was a numerical advantage towards improvement in NbM volume (mean +7.0 mm3 vs -6.4 mm3 for placebo) at week 16. No differences between treatment groups on these parameters were seen on the left side of the brain. This pattern of right-sided involvement aligns to regions of the BF believed to be most impacted in Lewy body disorders. In percentage terms, right BF volume was increased by 3.5 ± 2.5% with neflamapimod treatment and decreased by 4.2 ± 1.9% with placebo (p=0.028 for the difference). The change in right BF volume from the start to the end of the extension was 1.9 ± 3.8 mm3 (i.e., right BF volume was stable during the extension). There were no differences between placebo and neflamapimod during placebo-controlled period on functional connectivity measures. At the end of the extension, compared to the start of the extension, right BF to default mode network (DMN) static functional connectivity was significantly increased [baseline=0.130 (SD=0.58), increase=0.52, 95% confidence interval: 0.020, 0.084, p = 0.019 vs. start of extension]. In percentage terms, right BF to DMN static functional connectivity was increased during the extension by 46% (95% confidence interval:17.4%, 69.8%, p=0.014 vs. start of extension). Percent change in right BF to DMN static functional connectivity and change in CDR-SB during the extension were inversely correlated (p=0.027, r2=0.43), i.e. increase in functional connectivity was correlated to reduction (improvement) in CDR-SB. Neflamapimod is an investigational, orally administered small-molecule drug that readily crosses the blood-brain barrier and selectively inhibits the alpha isoform of p38 MAP kinase, a key driver of neuroinflammation and synaptic dysfunction. By targeting the critical disease processes underlying degenerative disorders of the brain, neflamapimod has the potential to reverse synaptic dysfunction, improve neuron health, and slow or prevent disease progression. Neflamapimod is currently in clinical development for the treatment of DLB, recovery after ischemic stroke, and primary progressive aphasia. In non-clinical studies, neflamapimod restored synaptic function within the BF cholinergic system, the brain region most affected in DLB. Across Phase 1 and 2 clinical trials involving more than 800 participants, the drug has been generally well tolerated and demonstrated consistent signals of efficacy. In the 91-patient Phase 2a AscenD-LB trial, neflamapimod significantly improved dementia severity and functional mobility in patients with DLB. Results from the 159-patient Phase 2b RewinD-LB trial, a 16-week randomized, double-blind, placebo-controlled trial followed by a 32-week open-label extension, further supported neflamapimod’s potential to deliver meaningful clinical benefit, improving both cognitive and functional outcomes and showing a positive effect on a key blood biomarker of neurodegeneration during the extension phase. Across both studies, the greatest benefits were observed in patients without AD co-pathology. Collectively, these findings underscore the therapeutic promise and scientific validity of neflamapimod as a potential treatment for DLB and other degenerative brain disorders.
