# GMP Production and Extended Toxicology of an Oral Formulation Drug for Alzheimer's Disease

> **NIH NIH U01** · NORTHWESTERN UNIVERSITY · 2024 · $1,546,636

## Abstract

ABSTRACT
Alzheimer’s disease (AD) and related dementias are a major global public health problem, predicted to increase
dramatically over the next decades. Effective therapies to prevent, cure, or slow the disease progression are
lacking. A diversified portfolio of new therapeutic strategies with discrete pharmacological function is urgently
needed. We propose repositioning of an existing acute brain injury clinical candidate, MW189, now in phase 2
critical care medicine testing for hemorrhagic stroke. Repositioning of therapeutic candidates in clinical
development, or repurposing of approved drugs, are generally considered faster and more efficient approaches
than de novo CNS drug discovery and development. Caveats include the lower success rates when done
across disease indications (e.g., oncology to neurology) vs within the same disease indication. Repositioning of
MW189 will use an existing CNS drug development portfolio and research infrastructure. Deliverables will allow
rapid transition to clinical evaluation in AD patients. MW189 is a CNS-penetrant, small molecule that selectively
attenuates stressor-induced changes in dysregulated cytokine production. The resultant pathophysiology
contributes to synaptic dysfunction, neurodegeneration and cognitive decline in diverse diseases. MW189 has
no liabilities in IND-enabling preclinical safety pharmacology and toxicology and successfully completed three
phase 1 clinical studies of safety, tolerability, pharmacokinetics and pharmacodynamic end point engagement.
MW189’s excellent profile in FDA guided preclinical and clinical studies provides a strong foundation for
continued MW189 clinical development in other CNS disease areas. We hypothesize that MW189 is a viable
candidate for daily oral treatment of dementia patients. We propose studies to remove the remaining technical
and regulatory barriers to MW189 entry into future AD clinical investigations.
Aim 1: Produce GMP clinical drug substance, drug product, reference standard and internal standard. GMP
clinical drug for oral administration will be FDA quality compliant for phase 2 INDs and will address recent FDA
new guidances on enhanced drug quality.
Aim 2: Perform extended GLP toxicology studies in rats (6 mo) and dogs (9 mo) with recovery phase and
toxicokinetics. Outcomes will allow future daily oral administration to AD patients and provide refined dosing
parameters for longer term administration.
Aim 3: Obtain a phase 2 IND for future clinical trials in early AD and related dementias. This final milestone will
position us to immediately proceed to a future phase 2a clinical study of AD patients.
Successful outcomes from the proposed investigations and the follow-on clinical trials will impact a number of
CNS disorders where cytokine dysregulation is part of the disease progression or susceptibility mechanism.

## Key facts

- **NIH application ID:** 10864940
- **Project number:** 5U01AG076480-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** LINDA J VAN ELDIK
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,546,636
- **Award type:** 5
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864940

## Citation

> US National Institutes of Health, RePORTER application 10864940, GMP Production and Extended Toxicology of an Oral Formulation Drug for Alzheimer's Disease (5U01AG076480-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10864940. Licensed CC0.

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