SMALL MOLECULE THERAPEUTIC FOR ALZHEIMER'S DISEASE

An estimated one out of eight individuals over the age of 65 has Alzheimer’s disease (AD), with a prevalence of 1-in-3 for those over age 85. There are approximately 5.8 million people in the USA with AD, with a global projection of over 150 million by 2050. There remains a lack of effective treatment to halt disease progression. Somatostatin receptor-4 (SSTR4) represents an innovative and viable brain target for AD treatment. A SSTR4 agonist has the potential to mitigate AD pathology via downstream enhancement of amyloid-beta metabolism, as well as the capacity to directly enhance cognitive function. This program seeks to advance a first-in-class SSTR4 agonist drug for AD treatment. The goal of this phase-I STTR is to establish an advanced lead SSTR4 agonist with optimized physiochemical attributes for enhancement of brain uptake. An optimization process based on SSTR4 structure-activity relationships has been undertaken. The approach is iterative and as 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, with synthesized compounds screened against through an iterative process. A successful candidate from this phase-I study will advance to the development phase, with GMP manufacturing of single candidate, full IND-enabling evaluations, and formulation for clinical trials. The IND preparation and FDA submission will precede clinical trials. This program demonstrates a clear intellectual property pathway for commercialization. The goal and aims of this study address priorities of National Institutes of Health, specific to PAR-19-317.