AD04 disease-modifying drug for Alzheimer's - preclinical and IND-enabling studies

PROJECT SUMMARY Alzheimer’s disease (AD) is like a medical time-bomb, poised to cripple the healthcare systems of the US and most other developed nations. Thus far, it is a disease with no cure that is affecting an increasingly large number of people, and has now become the sixth leading cause of death. The number of Americans living with Alzheimer's is growing, and growing fast. An estimated 6.7 million Americans age 65 and older were living with Alzheimer's in 2023. As the size of the U.S. population age 65 and older continues to grow, so too will the number and proportion of Americans with Alzheimer’s or other dementias. By 2050, the number of people age 65 and older with Alzheimer’s may grow to a projected 12.7 million, barring the development of medical breakthroughs to prevent or cure Alzheimer’s disease. The annual cost of care projected to reach $1.1 trillion. There are only two FDA-approved disease modifying therapeutics for AD. These monoclonal antibody drugs, aiming to clear amyloid deposits, are very expensive, have serious side effects and risks, require 12 to 24 infusions per year, and only modestly slow down disease progression. The other seven FDA-approved treatments for AD have limited effect for a short duration, and only serve to alleviate symptoms and do not treat the underlying cause of disease. There is a pressing need to develop better therapies to relieve the cognitive impairments of the disease and delay or even eliminate the need for the institutionalization of AD patients. The goal of the proposed project is to perform IND-enabling studies on a small molecule that is disease-modifying, low cost, requires only six subcutaneous injections per year and has a long safety record. This immunomodulating compound reduces brain inflammation and restores phagocytosis in the brain, and thus improves the clearance of amyloid. The efficacy of this molecule was discovered by serendipity when it was used in the control arm of a monoclonal antibody AD clinical study in Europe. Currently, six European countries have approved the start of Phase 2b clinical trials of this compound for Alzheimer’s, with the first patient enrolling in Austria in November 2023. In a pIND meeting with FDA, they requested an IND-enabling set of studies before clinical trials can be conducted in the US. In this Direct to Phase II SBIR proposal, ADvantage Therapeutics, Inc. will perform the studies recommended by the FDA and after their successful conclusion, and additional studies, if necessary, we will be poised to move forward with an IND submission. The proposed studies will help bring a novel cost-effective disease-modifying therapy to patients with AD.