An estimated one out of eight individuals over the age of 65 has Alzheimer's disease (AD), with aprevalence of 1-in-3 for those over age 85. There are approximately 5.8 million people in the USAwith AD, with a global projection of over 150 million by 2050. There remains a lack of effectivetreatment to halt disease progression. Somatostatin receptor-4 (SSTR4) represents an innovativeand viable brain target for AD treatment. A SSTR4 agonist has the potential to mitigate AD pathologyvia downstream enhancement of amyloid-beta metabolism, as well as the capacity to directlyenhance cognitive function. This program seeks to advance a first-in-class SSTR4 agonist drug forAD treatment. The goal of this phase-I STTR is to establish an advanced lead SSTR4 agonist withoptimized physiochemical attributes for enhancement of brain uptake. An optimization processbased on SSTR4 structure-activity relationships has been undertaken. The approach is iterative andas such each step informs the next with the data used to determine "go/no-go" advancement.Compound design and screening includes state of the art computer-aided drug design, withsynthesized compounds screened against through an iterative process. A successful candidatefrom this phase-I study will advance to the development phase, with GMP manufacturing of singlecandidate, full IND-enabling evaluations, and formulation for clinical trials. The IND preparation andFDA submission will precede clinical trials. This program demonstrates a clear intellectual propertypathway for commercialization. The goal and aims of this study address priorities of NationalInstitutes of Health, specific to PAR-19-317.
Public Health Relevance Statement: Alzheimer's disease (AD) is the most common type of dementia. Current medications have only
modest clinical benefit and do not modify the course of the disease. The goal of this program is to
advance a first-in-class somatostatin receptor subtype-4 agonist drug capable of mitigating AD
pathology.
Project Terms: <3'5'-cyclic ester of AMP>
<65+ years old> 