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.

Grant Number: 1R44AG091827-01
NIH Institute/Center: NIH
Principal Investigator: CARMELA ABRAHAM