Our Approach

Targeting Synaptic Dysfunction to Treat Neurodegenerative Disease

EIP Pharma is pursuing a new mechanism that is based on our understanding of how stress to the neuron, including that due to inflammation or amyloid plaques, leads to disease progression early in the neurodegenerative process.

Scientific evidence has shown that the enzyme p38 alpha is a driver of neurological disease progression. Chronic activation of p38 alpha in the brain interferes with how neurons signal to one another – this is called synaptic dysfunction. Synaptic dysfunction leads to memory loss and other cognitive deficits, and if left untreated will result in neuron death over time.

We are developing an oral therapy, neflamapimod, that inhibits the enzyme p38 alpha. We believe that if neflamapimod is given in the early stages of neurological disease, it may reverse synaptic dysfunction and improve neuron health. EIP is currently investigating neflamapimod in early-stage Alzheimer’s disease, Dementia with Lewy Bodies, and Huntington’s disease.

EIP Pharma licensed neflamapimod in 2014. A full chronic toxicology program of neflamapimod was completed, as well as phase 1 clinical trials and a preliminary evaluation in patients with rheumatoid arthritis prior to licensing.

After demonstrating the ability of neflamapimod to reverse synaptic dysfunction in animal models, the prior development experience allowed EIP Pharma to go directly to phase 2a clinical trials in patients with early-stage Alzheimer’s disease. EIP Pharma owns four issued US patents on the administration of neflamapimod to treat Alzheimer’s disease and other central nervous system (CNS) disorders and has filed for additional US and international patents.

We have evidence from two phase 2a clinical trials that neflamapimod reverses synaptic dysfunction and improves episodic memory, or a person's ability to create memories of new events and activities, in early-stage Alzheimer’s patients. A phase 2b study (REVERSE-SD) is currently underway to confirm these effects.

Treatment & Results

"Neflamapimod treatment showed improvement in memory tests that assess immediate and delayed recall in two phase 2a studies, strongly suggestive of reversal of synaptic dysfunction. With the demonstration of proof-of-mechanism and the definition of an optimal dose, neflamapimod is well positioned to demonstrate proof-of-concept on clinical cognitive endpoints in a subsequent study in patients with early Alzheimer's disease."

Professor Philip Scheltens, principal investigator for Study 302 and Director of the Alzheimer's Centre at the VU Medical Center