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Preclinical Results

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.

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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.

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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 along with Phase 2a results have been published in the journal Nature Communications. view the publication –  https://www.nature.com/articles/s41467-022-32944-3

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EIP Pharma Clinical Milestone Pipeline

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Pipeline

"The data from the trial of neflamapimod in DLB are very encouraging, 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 severe and progressive disorder."

Jeffrey L. Cummings, MD, ScD, Joy Chambers-Grundy Professor of Brain Science and Director of the Chambers-Grundy Center for Transformative Science, UNLV School of Integrated Health Sciences