A first-in-class orally bioavailable small molecule dual inhibitor targeting NLRP3 and the dopamine transporter to treat AD

ABSTRACTP2D Bioscience is developing a first-in-class treatment for Alzheimer’s disease (AD). Our
drug is an orally-effective combination that targets both innate immunity and the dopamine
transport (DAT) inhibitor. Recent studies suggest that TNFα and DAT inhibitors are orally
effective treatments for AD in preclinical AD transgenic mouse models.The proposed studies will determine if our compound is an effective treatment for AD using a
three transgenic animal models of AD. The rationale is rigorously evaluation for our lead
compound across different models of AD pathology in this limited direct-to-phase 2 SBIR
application. The proposed specific aims will determine if chronic oral treatment significantly
improves AD symptoms and AD /FTD pathophysiology in these animal models.Aim 1 : Determine the brain and plasma PK profile of our dual acting lead compound to aid
in developing a PKPD correlation.Aim 2: Determine the efficacy of chronic daily oral treatment of our dual acting lead
compound at improving cognitive/behavioral function in three transgenic models of dementia
and their AD-associated pathology