# Production and quality analysis of clinical drug for a novel CNS protein kinase inhibitor therapeutic candidate

> **NIH NIH R42** · NEUROKINE THERAPEUTICS, LLC · 2020 · $631,965

## Abstract

ABSTRACT
Alzheimer’s disease (AD) and related dementias are increasing rapidly yet, remarkably, there are no approved
disease modifying drugs. Virtually all trials targeting amyloid related pathways have failed over the last 10
years. Regrettably, few alternative targets or pathways have been explored. Therefore, there is an urgent need
to explore alternative pathways as monotherapies or as constituents of a multi-drug armamentarium for a
complex disease. An alternative view of progressive neurodegenerative disorders such as AD, frontotemporal
dementia, and Parkinson’s disease is diseases of progressive synaptic dysfunction. Protein kinase inhibitors
(PKI) are logical candidates to explore as potential attenuators of such progressive synaptic dysfunction and
cognitive decline. However, PKI drug candidates are under explored as a foundation for CNS disease-
modifying therapeutic development and there are currently no approved CNS PKI drugs for any indication. This
proposal is a discrete component of a clinical development campaign for a novel stress PKI drug candidate,
MW01-18-150SRM (= MW150) that represents a paradigm change for CNS targeted diseases such as AD.
MW150 is distinct from past or current drug candidates in AD clinical trials. MW150 ameliorates cognitive
dysfunction in discrete AD-relevant animal models. MW150 has a unique profile of target recognition,
pharmacological features, and efficacy outcomes. A GMP production scheme was developed and provided the
first released clinical drug supply for first-in-human (FIH) trials. This prior art provides a firm foundation for a
commercial scale production of GMP drug substance (API) and drug product (drug-in-capsule). There is an
immediate need for multi-Kg scale production of drug substance and validation of commercial drug product in
order to move into first-in-patient (FIP) status without untoward delays. In this regard, our specific aims are:
aim 1, develop and validate a large-scale production lot for GMP clinical drug substance (API); aim 2, generate
a pilot lot of. Completion of aim 1 is required immediately for the extended toxicology studies. Completion of
aims 1 and 2 allows immediate generation of the phase 2 IND quality (CMC) section and initiation of planning
for phase 2 FIP trials. The FIP trials will provide alternative therapeutic approaches to AD and related
dementia. The clinical campaign is directly testing the hypothesis that an isoform selective PKI drug can
address the synaptic dysfunction and injurious neuroinflammation that characterize diverse neurodegenerative
diseases. Further, attenuating the disease relevant pathways associated with increased p38aMAPK activity in
both neurons and glia tests the hypothesis that improved efficacy can be obtained with a single target drug that
works via pleiotropic drug action.

## Key facts

- **NIH application ID:** 9928391
- **Project number:** 5R42AG062095-03
- **Recipient organization:** NEUROKINE THERAPEUTICS, LLC
- **Principal Investigator:** Daniel Martin Watterson
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $631,965
- **Award type:** 5
- **Project period:** 2018-09-30 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928391

## Citation

> US National Institutes of Health, RePORTER application 9928391, Production and quality analysis of clinical drug for a novel CNS protein kinase inhibitor therapeutic candidate (5R42AG062095-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9928391. Licensed CC0.

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