R01AG074447

Phase 1 Clinical Trial of CMS121, a Novel Therapeutic Candidate for Alzheimer's Disease - 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 the 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 of 2020.

The clinical trial proposed in this application is the next step in evaluating CMS121 as a drug candidate for the treatment of AD.

Virogenics

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

California United States

State-Wide

Early Stage Clinical Trials for the Spectrum of Alzheimers Disease and Age-related Cognitive Decline (R01 Clinical Trial Optional) (PAR-18-877)

Amendment Since initial award the End Date has been extended from 08/31/23 to 05/31/24 and the total obligations have increased 112% from $2,503,169 to $5,303,779.