# First-in-human SAD & MAD trials for MW151, a novel Alzheimer's disease drug candidate that attenuates proinflammatory cytokine dysregulation

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $1,505,935

## Abstract

ABSTRACT
There are no approved disease-modifying drugs to prevent, delay, or slow disease progression of Alzheimer's
disease (AD) and related dementias. The overwhelming majority of AD clinical trials targeted the beta-amyloid
pathway with disappointingly ineffective outcomes in >99% of the studies. Therefore, there is an urgent need to
diversify the portfolio of disease modifying approaches that are distinct from prior art. Our unbiased discovery
strategy for the campaign described here focused on targeting a particular form of dysregulated inflammation,
injurious proinflammatory cytokine overproduction in the brain, that is a key contributor to synaptic dysfunction,
neurodegeneration and cognitive decline in diverse neurodegenerative diseases. We seek funding for the
required phase 1 clinical safety studies of MW01-2-151SRM (=MW151). MW151 is a novel, CNS-penetrant,
orally bioavailable, small molecule candidate that selectively suppresses stressor-induced proinflammatory
cytokine overproduction. MW151 ameliorates synaptic damage and cognitive impairment at low doses in
diverse animal models where proinflammatory cytokine dysregulation is established as a contributor to disease
progression. MW151 has no liabilities in investigational new drug (IND)-enabling safety pharmacology and
toxicology tests such as respiratory and cardiovascular safety pharmacology, rat and dog 28-day repeat
administration toxicology, and genotoxicity. The low risk aspect of MW151 safety is reinforced by an analog
developed for the demanding intravenous route of administration and its progression through phase 1a and
promising status in phase 1b. We hypothesize that MW151 will be a successful oral candidate for future
treatment of individuals with MCI/AD. This application seeks to progress through the required first-in-human
(FIH) safety clinical trials. Our specific aims are:
Aim 1: Conduct a first-in-human (FIH) phase 1a single ascending dose (SAD) study. This study will determine
safety and tolerability, maximum tolerated dose, and pharmacokinetics (PK) of MW151 in healthy adult
volunteers. Plasma cytokine levels will be measured to provide baseline data for a future exploratory
pharmacodynamic (PD) endpoint in phase 2a clinical trials.
Aim 2: Conduct a phase 1b multiple ascending dose (MAD) study of MW151. This study will determine safety
and tolerability, maximum tolerated dose, and PK of MW151 in healthy adult volunteers. In addition, a cohort of
elderly healthy subjects and exploratory PD inflammatory cytokine endpoints in CSF will be included.
Aim 3: Prepare clinical protocol and investigators brochure for a future phase 2a clinical trial of MW151 in early
AD. Based on the outcomes of the proposed phase 1 studies, we will design a phase 2a trial and prepare the
documents required. This will allow immediate progress to future FIP studies for AD.
Overall, MW151 represents a unique opportunity for development as a first-in-class disease-modifying
therapeutic.

## Key facts

- **NIH application ID:** 9852942
- **Project number:** 5R01AG061898-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** LINDA J VAN ELDIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,505,935
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852942

## Citation

> US National Institutes of Health, RePORTER application 9852942, First-in-human SAD & MAD trials for MW151, a novel Alzheimer's disease drug candidate that attenuates proinflammatory cytokine dysregulation (5R01AG061898-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9852942. Licensed CC0.

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