Evaluation of a dual PPAR agonist for treatment of Alzheimer's disease

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SUMMARY Alzheimer’s disease (AD) and related dementias are devastating conditions that affect millions of people, but no effective treatment options exist. Studies are currently being performed as part of the funded Phase II STTR parent award to test efficacy of a potential AD therapeutic, OL-003, in two additional animal models and assess pharmacology and toxicology. The overarching goal of the Phase II project is to generate data that is required to submit an Investigational New Drug (IND) package to the FDA for clinical trials approval. Due to budget limitations, critical studies needed for IND approval were not able to be proposed. Therefore, this administrative supplement seeks to generate additional pharmacokinetic (PK) data within the scope of the parent project that will contribute to a more complete IND package. In this administrative supplement, two aims are proposed. In aim 1, PK analysis of two different formulations of OL-003 will be performed in mice to identify the optimal formulation to be used in IND-enabling studies and Phase 1 clinical trials. The formulations, consisting of FDA approved adjuvants/excipients that have been shown to enhance the PK profile of brain-acting drugs, will be compared head-to-head to identify improvements in solubility and brain distribution of OL-003. In aim 2, OL-003 PK linearity and tissue distribution will be assessed with increasing dose. Steady state of OL-003 in the brain will be determined by repeated daily dosing in mice using the selected formulation from aim 1. These data will support the optimal OL-003 dosing strategy to maintain a safe and therapeutic brain exposure for the treatment of AD. The results from this administrative supplement will strengthen the IND application and decrease the time to OL-003 first-in-human trials.