CervoMed Inc. announced the publication online on September 1, 2023, in Neurology®, the medical journal of the American Academy of Neurology, of additional pre-specified analyses of the AscenD-LB Phase 2a clinical trial showing an association between plasma phosphorylated tau at position 181 (ptau181) levels at study entry and patient's response to neflamapimod in the treatment of dementia with Lewy Bodies (DLB). The AscenD-LB clinical trial was a Phase 2a double-blind, placebo-controlled, 16-week treatment study of neflamapimod in 91 patients with mild-to-moderate DLB (NCT04001517). The main results, which were published in September 2022 in the journal Nature Communications, demonstrated that neflamapimod significantly improved dementia severity compared to placebo and also showed significant improvement on motor function compared to placebo; at the highest dose evaluated, neflamapimod also improved cognition.

For the Neurology publication, as pre-specified in the protocol, after the study was completed (i.e., post-hoc), with the availability of information regarding the utility of the assay to identify patients with Alzheimer disease (AD) co-pathology in patients with DLB, pre-treatment plasma ptau181 levels were determined in patients who had at least one on-study efficacy measure and participants were grouped based on a cut-off for AD pathology of 2.2 pg/mL (established in a separate cohort to identify AD from healthy controls). Clinical outcomes for the comparison of placebo with neflamapimod 40mg three-times-daily (TID), the higher and more clinically active of two doses studied, were analyzed utilizing Mixed Models for Repeated Measures within each sub-group (baseline plasma ptau181 < and =2.2 pg/mL). The results, as reported in the current publication, showed 45 participants were below, and 40 above, the 2.2 pg/mL cut-off at baseline.

Moreover, during the 16-week treatment period, in the comparison of placebo with neflamapimod 40mg TID, for all endpoints evaluated, improvements with neflamapimod treatment were greater in participants below the cut-off, compared with that in those above the cut-off. In addition, participants below the ptau181 cut-off at baseline showed significant improvement over placebo in an Attention Composite measure (+0.42, 95%CI: 0.07?0.78, p=0.023, Cohen's d effect size=0.78), the Clinical Dementia Rating Scale Sum of Boxes (-0.60, 95%CI:-1.04,-0.06, p=0.031, d=0.74), the Timed Up and Go test (-3.1 sec, 95%CI:-4.7,-1.6, p<0.001, d=0.74), and International Shopping List Test-Recognition (+1.4, 95% CI: 0.2?2.5, p=0.024, d=1.00).