Research Project
8278498
DESCRIPTION (provided by applicant): PD2007 is a selective DAT inhibitor that P2D Bioscience (P2D) is developing for the treatment of obesity. PD2007 is an analog of benztropine (Cogentin) a non-Scheduled, safe FDA-approved drug in clinical use for over 40 years. Structure-activity-relationship studies were conducted to improve PD2007 efficacy while decreasing side-effects. Our SBIR Phase 1 data demonstrate that PD2007 produces sustained weight-loss and decreased body fat. PD2007 appears to decrease body weight by increasing energy expenditure, a novel mechanism of action. PD2007 is radically different from the non-selective DAT inhibitor, amphetamine, a potent anti-obesity drug: For example: 1. PD2007-induced weight-loss appears due to increased energy expenditure unlike the appetite suppressant amphetamine 2. PD2007 is not addicting; amphetamine is an addicting Schedule II drug of abuse 3. PD2007 does not affect blood pressure or heart rate; amphetamine significantly increases both 4. PD2007 is not a stimulant; amphetamine is a widely used stimulant 5. PD2007's pharmacokinetics are consistent with once a day dosing while amphetamine requires multiple daily dosing for efficacy. The purpose of the proposed SBIR Phase 2: 1) Aim 1 will further assess whether PD2007 has a novel mechanism of action in inducing weight-loss - enhanced energy expenditure, and 2) Aims 2, 3, 4 and 5 represent preclinical safety studies responsive to FDA-guidance ICH M3 for the successful submission of a PD2007 Investigational New Drug (IND) application. This IND would allow clinical testing of PD2007 in humans. Specifically: Aim 1: Determine if PD2007-induced weight-loss is associated with increased energy expenditure, lipolysis and/or glycogenolysis. Aim 2: Assess PD2007 genotoxicity. Aim 3: Assess PD2007 absorption, distribution, metabolism and excretion (ADME). Aim 4: Assess oral PD2007 safety pharmacology in three studies. Aim 5: Assess repeated PD2007 dose toxicity in rats.
