Research & Development
EIP Pharma Publishes Translational Data of Preclinical and Phase 2a Results for Neflamapimod in Dementia with Lewy Bodies: Nature Communications
23 September 2022 - - An article in Nature Communications shows translational results from preclinical animal models to an exploratory, placebo-controlled clinical trial of neflamapimod in patients with mild to moderate Dementia with Lewy Bodies, US-based private clinical stage biopharmaceutical company EIP Pharma Inc said.

The findings in "Preclinical and Randomized Clinical Evaluation of the p38α Kinase Inhibitor Neflamapimod for Basal Forebrain Cholinergic Degeneration" demonstrate that neflamapimod's unique mechanism of action has the potential to improve cognitive and motor function in patients with neurodegenerative diseases affecting the basal forebrain cholinergic system, such as DLB.

Neflamapimod, which has been granted Fast Track status as a treatment for DLB by the US Food and Drug Administration, is an oral, brain-penetrating small molecule that selectively targets and inhibits within the neuron the enzyme p38 MAP kinase alpha, which is known to regulate Rab5, a key protein implicated in the underlying disease process of neural degeneration in the basal forebrain.

The animal studies in the publication show that neflamapimod reduces Rab5 activity and reverses the neurodegenerative process in the basal forebrain.

The pre-clinical data were translated into the clinic in an exploratory Phase 2a clinical trial in DLB patients in which neflamapimod was shown to be generally safe and well tolerated, and improved versus placebo the dementia, as assessed by the gold standard dementia rating scale, and motor function.

These combined pre-clinical and clinical results provide a foundation for a confirmatory, hypothesis-testing Phase 2b clinical study evaluating neflamapimod for DLB.

The basal forebrain is the primary source of cholinergic neural stimulation in the brain, and its degeneration occurs in aging and neurodegenerative disease-related cognitive disorders, including Dementia with Lewy Bodies, the second most common form of neurodegenerative dementia. In DLB, dysfunction in the basal forebrain cholinergic neuron is an important driver of disease expression and progression.

Recent studies have also demonstrated that BFCN loss underpins gait dysfunction in Parkinson's Disease.

Correcting the functional deficit in the cholinergic system amplifies the release of acetylcholine and has the potential to alter the course of the neurodegeneration that drives a number of devastating brain diseases.

Neflamapimod is an investigational oral, brain-penetrating small molecule drug that inhibits the intra-cellular enzyme p38MAP kinase alpha (p38α which is expressed in neurons under conditions of stress and disease.

P38α plays a major role in inflammation-induced synaptic toxicity, leading to impaired synaptic function. In pre-clinical studies, neflamapimod reverses synaptic dysfunction, including within the part of the brain most affected by Dementia with Lewy bodies the basal forebrain cholinergic system.

Results from the AscenD-LB Phase 2a clinical study demonstrated neflamapimod significantly improved cognition and function as measured by the gold standard dementia rating test, the Clinical Dementia Rating Sum-of-Boxes (CDR-SB), and also showed significant impact on motor function as measured by the Timed Up and Go test.

In addition, at 40mg TID, the higher of two doses in the study, neflamapimod improved outcomes on a cognitive test battery ("Neuropsychological Test Battery," NTB) designed to evaluate the cognitive domains most prominently impacted in DLB, attention and executive function.

Neflamapimod is the first treatment that shows potential impact on cognition, function and motor function in patients with DLB.

The combined pre-clinical and clinical data are consistent with neflamapimod treating the underlying disease process and having the potential to be the first disease-modifying treatment for DLB.

EIP Pharma is a private, clinical-stage biotechnology company advancing CNS-focused therapeutics to benefit patients with a range of debilitating neurodegenerative diseases with significant unmet patient need.

The company is focused on the potential of neflamapimod, an investigational compound being evaluated for its potential to treat synaptic dysfunction, the reversible aspect of the underlying neurodegenerative processes that cause disease in Dementia with Lewy Bodies and certain other major neurological disorders.
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