R01AG071810

First-in-Human (Phase 1) Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of IBC-AB002 in Persons with Early Alzheimer's Disease (AD) - Abstract

Alzheimer's Disease (AD) and related dementias are heterogeneous multifactorial diseases, in which many etiopathogenic mechanisms are involved, eventually leading to neuronal death and loss of cognitive function.

Numerous attempts are made to arrest the disease, or to slow down its progression by directly targeting its major hallmarks - amyloidosis, pathological neurofibrillary tangles, and local neuroinflammation; none have shown major clinical improvement to date.

A novel, paradigm-shifting approach for treating AD and other neurodegenerative disorders is to harness the body's own mechanisms of maintenance and repair. Among such common pathways is the systemic immune response, which has been shown to display supportive effects on brain maintenance, plasticity, and repair.

Studies initiated by the laboratory of Prof. Michal Schwartz at the Weizmann Institute of Science in Israel and supported by others, over two decades, have illuminated our understanding of the intricate relationships between the brain and the peripheral immune system, and have demonstrated the potential for benefit of leveraging the brain-immune relationship for the treatment of AD and neurodegeneration.

Immunobrain Checkpoint (IBC) is proposing to conduct a First-in-Human (FIH) study in AD using its novel immunotherapy approach of targeting the peripheral immune system by transient blockade of the inhibitory immune checkpoint, programmed death-ligand 1 (PD-L1).

The pre-clinical pharmacological studies with various mouse models for AD and dementia revealed that single antibody administration was sufficient to evoke a cascade of events leading to a reduction in brain pathology and restoration/maintenance of cognitive abilities. These studies indicated that the therapeutic disease-modifying effect of anti-PD-L1 antibody administration requires intermittent repeated injections of a short-lived antibody with long intervals between successive injections.

These observations set the basis for IBC's uniquely engineered antibody, IBC-AB002, and for the proposed FIH clinical study design.

IBC is proposing to conduct a FIH study to evaluate the safety, tolerability, and pharmacokinetics and preliminary exploratory activity of IBC-AB002 in persons with early AD. The planned study will be a randomized, double-blind, placebo-controlled study of escalating multiple IV doses, combining single- and multiple-ascending dose components.

The study will have an adaptive design and will be carried out in 2 parts. Part A will comprise a single-ascending-dose (SAD) study and Part B will continue dosing of Part A subjects as a multiple-ascending-dose (SAD) study, with 12 weeks interval between administrations.

Data emerging from this study will be used to support decisions regarding further clinical development of IBC-AB002, most importantly the setting of dose, dose interval, and biomarker collection strategy for any future Phase 2 studies.

Immunobrain Checkpoint

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]

New York 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 total obligations have increased 190% from $1,984,624 to $5,749,685.