December 16, 2020

EIP Pharma Announces Publication of Preclinical Results Demonstrating Potential of Neflamapimod to Promote Functional Recovery after Ischemic Stroke

Administration of neflamapimod during the subacute phase after transient ischemia induced stroke in rats promoted functional recovery

 Associated increased levels of brain-derived neurotrophic factor (BDNF) suggest the effects were mediated by increasing synaptic plasticity

Boston, Mass., December 16, 2020 – EIP Pharma, Inc. (, a CNS-focused therapeutics company, announced today the scientific publication of preclinical results that demonstrate neflamapimod promotes functional recovery after ischemic stroke in rats. Entitled “Continuous administration of a p38α inhibitor during the subacute phase after transient ischemia-induced stroke in the rat promotes dose-dependent functional recovery accompanied by increase in brain BDNF protein level,” the report was published in the journal PLOS ONE.

In the study neflamapimod was administered to rats at either 1.5 mg/kg or 4.5 mg/k twice daily for six weeks, starting 48-hours after stroke was induced via transient middle cerebral artery occlusion. The major findings showed that neflamapimod treatment, relative to vehicle treatment:

  • Significantly improved, relative to vehicle treatment, behavioral outcomes assessed by the modified neurological severity score (mNSS) at Week 4 and at Week 6 post stroke in a dose-dependent manner (p<0.001).
  • Demonstrated significant beneficial effects, relative to vehicle treatment, on specific measures of sensory and motor function (p<.001 on all measures).
  • Resulted in a dose-related statistically significant increase relative to vehicle treatment in brain-derived neurotrophic factor (BDNF) protein levels in the brain, a previously reported potential marker of synaptic plasticity.

“While thrombolysis and thrombectomy have significantly improved the outcome for patients with acute ischemic stroke, because they are only effective when administered within the first small number of hours after the stroke, most patients are not eligible for such treatment.   Combined with the failure of numerous other approaches to neuroprotection, there is growing interest in developing therapies to promote functional recovery after the completion of the acute stroke event,” said John Alam, MD, the senior author of the publication and CEO of EIP Pharma.

Along with demonstrating the potential of neflamapimod to promote functional recovery through enhancing synaptic plasticity, the results of this study offer the possibility of having a therapy for stroke that could be initiated outside the short time window for neuroprotection. From a drug development perspective, starting treatment in a clinical study at 48 hours or later after stroke allows for the inclusion of more homogenous sub-populations of patient, thereby increasing the statistical power of clinical studies to detect treatment effects. As a result, the company believes definitive clinical-proof-of-concept could potentially be demonstrated with a less than 200-patient phase 2 clinical study that would evaluate the effects on functional recovery of three months neflamapimod treatment, starting in the first week after an acute ischemic stroke.

About Neflamapimod

Neflamapimod is an investigational drug that is a brain-penetrant, oral small molecule that inhibits the intra-cellular enzyme p38 MAP kinase alpha (p38α). P38α, which is expressed in neurons under conditions of stress and disease, plays a major role in inflammation-induced synaptic toxicity, leading to impairment of synaptic function. Synaptic dysfunction is known to be a major drive of the cognitive and functional deficits function seen in many CNS diseases. Results of the AscenD-LB Phase 2 clinical study that demonstrated proof-of-concept for neflamapimod as a treatment for dementia with Lewy bodies (DLB) were recently presented at the 13th Clinical Trials in Alzheimer’s Disease (CTAD) Meeting Nov 4-7, 2020).  In that study, neflamapimod significantly improved cognition, as assessed by a DLB-specific Neuropsychological Test Battery designed to evaluate attention and executive function.  In addition, the cognitive effects of neflamapimod appeared to be clinically meaningful, with a statistically significant effect on the Timed Up and Go Test and encouraging trends on other secondary clinical endpoints.

About Recovery After Ischemic Stroke

Approximately 800,000 individuals in the US suffer an acute stroke every year, of which 85 to 90 percent are due to ischemia (reduced blood flow due to occlusion of one of the blood vessels into the brain).   While recovery is full or near complete recovery can be expected in patients with a mild stroke, the 30 to 50 percent of patients with moderate, moderate-severe, or severe stroke generally have residual, often prominent disability at 3 months and 12 months after the acute event.  As a result, stroke is the number one cause of physical disability in adults in the US.

About EIP Pharma Inc

EIP Pharma, Inc. is a private, Boston, MA-based company advancing CNS-focused therapeutics to benefit patients with neurodegenerative diseases.

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Alam JJ, Krakovsky M, Germann U, Levy A (2020) Continuous administration of a p38α

inhibitor during the subacute phase after transient ischemia-induced stroke in the rat promotes dose dependent functional recovery accompanied by increase in brain BDNF protein level. PLoS ONE 15(12): e0233073.




Noel Donnelly 



Lissette Steele


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