# Phase 1 Clinical Trial of CMS121, a Novel Therapeutic Candidate for Alzheimer's Disease

> **NIH NIH R01** · VIROGENICS, INC. · 2022 · $2,338,814

## Abstract

Abstract
 Our goal is to conduct a Phase I clinical trial of CMS121, a small molecule that has shown efficacy in
multiple mouse models of Alzheimer's Disease (AD) and which affords a different therapeutic approach for
treatment of AD in humans.
 There are currently no drugs or other therapeutic interventions that can reverse or halt the
progression of Alzheimer's disease (AD). The need for a fundamental rethinking of the way clinical
candidates for AD are chosen and tested is exemplified by the large number of clinical trial failures for
potential AD therapeutics. An effective AD drug will have to demonstrate powerful effects against multiple
pathological processes. A truly disease-modifying drug with long-term therapeutic benefits and immediate
cognitive benefits would be a tremendous benefit to the millions affected by AD. CMS121 was derived from
a different approach to an AD therapeutic and does not directly interact with the targets of the failed drug
candidates, thereby providing an altogether new AD drug candidate.
 The product was developed in conjunction with Salk Institute scientists for treatment of Alzheimer's
Disease (AD). The parent compound, identified from a broad screen of compounds for neuroprotective
activity, was modified to obtain a series of derivatives with vastly superior protective and pharmacologic
characteristics. The derivative, CMS121, prevents and reverses a number of the symptoms associated
with AD in both genetic and sporadic mouse models of AD.
 Studies of the mechanism of action show CMS121 affects multiple, specific regulators of lipid
synthesis and metabolism, resulting in reduction of fatty acid synthesis and lipid peroxidation. Both of
these features are elevated in AD brains with the increased levels associated with neuroinflammation.
Inhibition or removal of these regulators of lipid synthesis and metabolism has been shown to be beneficial
in mouse models of AD.
 Currently, the IND-enabling studies are in the final stages. Large scale GMP manufacture has been
completed and sufficient product is ready for clinical trial. The product has been tested for stability under a
variety of conditions, genotoxicity, absorption, distribution, metabolism and excretion. The last toxicology
and pharmacology studies in rats and dogs are nearing completion. The FDA has been notified of our
intent to file an IND application and has assigned Virogenics an IND number for CMS121. Submission of
the IND application is on target for the fourth quarter 2020. The clinical trial proposed in this application is
the next step in evaluating CMS121 as a drug candidate for treatment of AD.

## Key facts

- **NIH application ID:** 10485245
- **Project number:** 5R01AG074447-02
- **Recipient organization:** VIROGENICS, INC.
- **Principal Investigator:** Pamela Anne Maher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,338,814
- **Award type:** 5
- **Project period:** 2021-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485245

## Citation

> US National Institutes of Health, RePORTER application 10485245, Phase 1 Clinical Trial of CMS121, a Novel Therapeutic Candidate for Alzheimer's Disease (5R01AG074447-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10485245. Licensed CC0.

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