# A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients with Mild-to-Moderate Dementia with Lewy Bodies (DLB)

> **NIH NIH R01** · EIP PHARMA, INC. · 2024 · $8,066,994

## Abstract

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after
Alzheimer’s disease (AD). DLB is a more rapidly progressive disease than AD, with a median time from diagnosis
to death or nursing home admission that is half that seen in AD and is associated with extensive burden on both
patients and family caregivers. There is a great unmet medical need, with no approved treatments, only AD and
Parkinson’s disease (PD) drugs used off-label to partially or temporarily relieve some of its severe cognitive and
motor symptoms. The proposed treatment, neflamapimod, an orally bioavailable, highly specific inhibitor of the
intracellular enzyme p38 mitogen activated protein kinase alpha (p38α), is in clinical development by EIP Pharma
with a phase 2a study in DLB and phase 2 studies in early AD already completed. Preclinical data indicate that
neflamapimod, through inhibiting p38α, therapeutically targets specific pathogenic mechanisms underlying
dysfunction and degeneration of neurons in a part of the brain called the basal forebrain, abnormalities in which
are considered to be the major pathogenic drivers of the dementia in DLB. For example, neflamapimod increased
the number of functioning basal forebrain cholinergic neurons in Ts2 transgenic mice that, along with modeling
Down syndrome, develop neurodegeneration in the basal forebrain cholinergic system. Together, such evidence
provides a strong scientific rationale for neflamapimod as a disease modifying treatment for DLB. In accordance
with this, neflamapimod received Fast-Track designation by the FDA for DLB. A recently completed phase 2a
exploratory (i.e., hypothesis-generating) clinical trial (NCT04001517) in 91 patients with mild-to-moderate DLB,
also receiving cholinesterase inhibitor therapy, provided preliminary evidence of clinical efficacy of neflamapimod
on various cognitive, motor, and functional aspects of the disease. The proposed phase 2b trial will confirm and
expand upon these results. The Specific Aims are to, in the context of performing a phase 2b randomized,
double- blind, placebo-controlled, 16-week treatment study of neflamapimod (40mg TID) in 160 subjects with
mild-to-moderate DLB: (Aim 1). Demonstrate that neflamapimod improves cognition and function, based on
primary (Neuropsychological Test Battery) and secondary (Clinical Dementia Rating Scale sum of boxes, Timed
Up and Go test, The Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change) efficacy
measures in patients with mild-to-moderate DLB receiving cholinesterase inhibitors; (Aim 2). Assess
neuropsychiatric outcomes and safety/tolerability during treatment with neflamapimod in patients with DLB; and
(Aim 3). Assess effects of neflamapimod on electroencephalographic (EEG) measures of DLB, specifically beta
functional connectivity and alpha-reactivity; both markers of basal forebrain cholinergic dysfunction. Successful
completion of this phase 2b trial will inform ...

## Key facts

- **NIH application ID:** 10765662
- **Project number:** 5R01AG080536-02
- **Recipient organization:** EIP PHARMA, INC.
- **Principal Investigator:** John Alam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $8,066,994
- **Award type:** 5
- **Project period:** 2023-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765662

## Citation

> US National Institutes of Health, RePORTER application 10765662, A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients with Mild-to-Moderate Dementia with Lewy Bodies (DLB) (5R01AG080536-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10765662. Licensed CC0.

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