# 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 · $250,000

## Abstract

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after
Alzheimer’s disease (AD). It is rapidly progressive, with a median time from diagnosis to death or nursing home
admission that is half that seen in AD, with extensive burden on 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
the basal forebrain, considered to be the major pathogenic drivers of dementia in DLB, e.g., increasing the
number of functioning basal forebrain cholinergic neurons in Ts2 transgenic (Down syndrome) mice that develop
neurodegeneration in the basal forebrain cholinergic system. With a strong scientific rationale for neflamapimod
as a disease modifying treatment for DLB, neflamapimod received Fast-Track designation by the FDA for DLB.
A completed phase 2a exploratory (i.e., hypothesis-generating) clinical trial (NCT04001517) in 91 patients with
mild-to-moderate DLB provided preliminary evidence of clinical efficacy of neflamapimod on various cognitive,
motor, and functional aspects of the disease. The current funded project (R01AG080536) conducts a phase 2b
trial to 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 DLB: (Aim 1). Demonstrate that neflamapimod improves cognition and function, based on
primary (Clinical Dementia Rating Scale Sum of Boxes) and secondary (Timed Up and Go test, a
Neuropsychological Test Battery, The Alzheimer’s Disease Cooperative Study – Clinical Global Impression of
Change) efficacy measures in patients with mild DLB; (Aim 2). Assess neuropsychiatric outcomes and
safety/tolerability during neflamapimod treatment in these subjects; and (Aim 3). Assess effects of neflamapimod
on electroencephalographic (EEG) measures of DLB, markers of basal forebrain cholinergic dysfunction. Newly
added Aim 4 assesses a proposed biomarker of therapeutic activity in the basal forebrain by structural and
functional MRI. Successful completion of this phase 2b trial will inform our pivotal phase 3 trial, advancing
neflamapimod as a disease-modifying treatment for DLB and providing hope for these patients and their families.

## Key facts

- **NIH application ID:** 11127000
- **Project number:** 3R01AG080536-02S1
- **Recipient organization:** EIP PHARMA, INC.
- **Principal Investigator:** John Alam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2023-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11127000

## Citation

> US National Institutes of Health, RePORTER application 11127000, A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients with Mild-to-Moderate Dementia with Lewy Bodies (DLB) (3R01AG080536-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11127000. Licensed CC0.

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