Brain Disease Frontal Lobe Illustration

Un estudio muestra que el neflamapimod tiene potencial para mejorar la función cognitiva en pacientes con enfermedades neurodegenerativas

EIP Pharma publica datos traslacionales de resultados preclínicos y de fase 2a para Neflamapimod en demencia con cuerpos de Lewy.

  • Neflamapimod demuestra que invierte el proceso neurodegenerativo en el sistema colinérgico del prosencéfalo basal en modelos animales.
  • Los datos de fase 2a en demencia con cuerpos de Lewy muestran efectos positivos de neflamapimod en los criterios de valoración clínicos asociados con la función neuronal colinérgica.
  • EIP Pharma planea el inicio de un ensayo clínico de fase 2b confirmatorio para DLB.

Una compañía biofarmacéutica privada en etapa clínica centrada en el desarrollo de terapias de investigación para enfermedades del SNC con necesidades significativas de los pacientes, EIP Pharma Inc., anunció hoy (21 de septiembre) la publicación de un artículo en

Ralph A Nixon, MD, PhD, Director of the Center for Dementia Research at the Nathan S. Kline Institute for Psychiatric Research in Orangeburg NY and senior author on the publication, commented, “We are pleased to report on the finding of a major translational step forward towards a therapy that treats cholinergic degeneration in the basal forebrain. We hypothesized that neflamapimod would achieve this therapeutic objective because it inhibits p38a kinase, an enzyme known to regulate activity of a central player in the pathogenic process underlying cholinergic degeneration, the endosome-associated protein Rab5. Indeed, in an animal model, neflamapimod reduced Rab5 activity and reversed the neurodegenerative process in the basal forebrain.

“Furthermore, in the placebo-controlled clinical trial of neflamapimod in DLB patients, the beneficial effects on cognition and motor function are consistent with neflamapimod treating the cholinergic deficit that underlies the clinical presentation of DLB. Taken together, the findings indicate that neflamapimod appears to represent a scientific breakthrough towards treating degeneration of the basal forebrain cholinergic system, a long-standing objective of drug development for a range of neurodegenerative diseases.”

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 (DLB), the second most common form of neurodegenerative dementia. In DLB, dysfunction in the basal forebrain cholinergic neuron (BFCN) 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.

“With this unique mechanism that treats cholinergic neuronal degeneration, in vivo preclinically and clinically in DLB patients, we strongly believe in neflamapimod’s potential to play an important role in the treatment of neurodegenerative diseases, especially in DLB where cholinergic dysfunction contributes to both the cognitive deficits and gait dysfunction that together make this a particularly debilitating disease,” said John Alam, MD, scientific founder, and Chief Executive Officer of EIP Pharma.

“The cholinergic system has long been known to be critical in the pathogenesis of dementia, and neflamapimod’s profile is well suited to become a foundational treatment in a disease like DLB, where there are no approved therapies. The data published today provide us confidence to progress neflamapimod into a confirmatory Phase 2b clinical trial in Dementia with Lewy Bodies.”

Reference: “Preclinical and Randomized Clinical Evaluation of the p38a Kinase Inhibitor Neflamapimod for Basal Forebrain Cholinergic Degeneration” by Jiang, Y., Alam, J.J., Gomperts S.N. et al., 21 September 2022, Nature Communications.
DOI: 10.1038/s41467-022-32944-3

About Neflamapimod

Neflamapimod is an investigational oral, brain-penetrating small molecule drug that inhibits the intra-cellular enzyme p38MAP kinase alpha (p38a), which is expressed in neurons under conditions of stress and disease. P38a 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 (DLB) – 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 (TUG). 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.

About EIP Pharma

EIP Pharma, Inc. 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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