EIP Pharma has conducted neﬂamapimod preclinical studies in animal models. In these models, neﬂamapimod improved neurological outcomes, supporting its use to treat neurological disorders in human patients.
In aged rats with identiﬁed cognitive deﬁcit, neﬂamapimod improved cognitive performance (p=0.007), as assessed in a maze test. The aged rat model was chosen to evaluate neﬂamapimod because the cognitive deﬁcits in that model are due to inﬂammation-induced synaptic dysfunction.
Neﬂamapimod was also studied in a rat stroke model. Neﬂamapimod administered for a duration of six weeks after the stroke led to multiple improved parameters of neurologic function compared to control (p < 0.001 for each of global neurologic scores, motor- and sensory-speciﬁc tests). Recovery after stroke is largely dependent on neuronal and synaptic plasticity, thus these results support our hypothesis that neﬂamapimod can reverse synaptic damage.
To address its ability to preserve cholinergic neurons, neflamapimod was tested in Ts2 transgenic mice, that model Down syndrome (DS) and also develop a neurodegenerative pathology including basal forebrain cholinergic degeneration and endosomal pathology. Neflamapimod treatment for one month beginning at approximately six months of age reversed the neurodegenerative phenotype, restoring choline acetyltransferase positive neuron (i.e. cholinergic neuron) counts in the medial septal nucleus (MSN) to levels comparable to those in wildtype. Also reversed by neflamapimod treatment in Ts2 mice were endosomal abnormalities, as indicated by cortical counts of medium and large Rab5+ early endosomes.
The results of this preclinical study have not yet been published, but were presented at the 2019 Alzheimer’s Association International Conference.
"The data from the trial of neflamapimod in DLB are very encouraging. Not only was the prespecified primary outcome met for the three times daily dose arm but supportive trends were observed in several of the secondary outcomes, setting the stage for more extensive testing. There are no approved treatments for DLB, the second most common cause of neurodegenerative dementia, and there is an urgent need to find therapies for this and related disorders such as Alzheimer's disease."