U01AG082687

Completion of non-clinical long-term GLP safety and GMP manufacture for first-in-class neuron regenerative therapy, NNI-362 phase 2 POC AD trial - project summary.

Neuronascent (NNI) discovered a unique therapy for Alzheimer's, NNI-362, that promotes adult-born neurons to replace lost neurons, while protecting from degeneration. In NNI's completed phase 1A trial, NNI-362 demonstrated safety and significant reduction of brain phosphotau181. The aim is to follow up the phase 1A with a phase 2 trial in AD, for which the following 4 specific aims are necessary.

1) NNI requires further GMP manufacture and 2) liquid-gel cap formulation of NNI-362; 3) the long-term (6-months) safety in M/F rats and dogs; and 4) regular IND updates and a meeting with FDA to discuss the phase 2 clinical plan.

This unique drug could be beneficial for AD by limiting phosphotau pathology and promoting new neurons to reverse disease over a six-month period.

In the first aim, Onyx Scientific will scale-up NNI-362 from the 1 kg CGMP method used for phase 1A, to the >5 kg CGMP required for completion of phase 2-3. Secondly, NNI-362 clinical product will then be formulated into a liquid-gel capsule prepared at 120 mg/capsule, already shown safe and potentially efficacious in aged subjects. Patheon prepared the formulation used in phase 1A, and determined the practicality of the liquid-gel cap with NNI-362.

Thirdly, Charles River will complete a dog and rat (M/F) GLP safety testing for 6-months, as required by FDA for treatment of humans for the same 6-month period. The doses will be the same as the completed 14-day/14-day washout study in rats at 10, 50 and 150 mg/kg and in dogs at 15, 45 and 210 mg/kg PO daily. Charles River has considerable experience in carrying out FDA-approved GLP safety studies.

Lastly, regulatory contractors CCS Associates will provide yearly regulatory IND-update filings and will request a FDA meeting to discuss the phase 2 clinical trial plan for mild to moderate AD patients.

With decades of AD drug failures, NNI used human neural cell screen to discover a "neuron generating and neuroprotective" drug. Pre-clinical studies of NNI-362 demonstrated new hippocampal neurons in aging and disease models, and neuroprotection to allow new neuron integration that reversed behavioral deficits. Phase 1A in healthy aged subjects demonstrated safety and indicated that NNI-362, provided significant reduction of AD-progression marker phosphotau181 after only 16 days of treatment period in human aged subjects. With longer-term treatment of AD patients, NNI-362 has the potential to not only slow progression of AD over the short-term, but promote new neurons to fully reverse disease, long-term.

Neuronascent

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]

Maryland United States

State-Wide

Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional) (PA-20-272)

Amendment Since initial award the End Date has been extended from 08/31/25 to 02/28/26 and the total obligations have increased 116% from $2,100,000 to $4,543,556.