Novel CEHC Derivatives for Neuroinflammation

Experimental studies conducted under an SBIR Phase I (SBIR I) Grant, 1 R43 AG023510, have identified a compound that is a potential treatment for Amyotrophic Lateral Sclerosis (ALS). Encore Pharmaceuticals, Inc. (EncorePharma ) holds a composition of matter patent for the compound. The compound's mode of action in in vitro testing and its activity in preliminary studies in the G93A-SOD1 mouse model of ALS, suggest it may be the first drug candidate to have an overall impact on ALS disease progression. This SBIR Phase II Application (SBIR II) seeks support to further preclinical development of the compound in preparation for submission of an Investigational New Drug (IND) Application to the FDA, allowing initiation of clinical trials with the compound. The important preclinical development work defined in this SBIR II is the first step in commercialization of a potentially important new pharmaceutical agent. The successful scientific/business collaborations with the Oklahoma Medical Research Foundation (OMRF) in SBIR I will be further cultivated in SBIR II. The SBIR II Specific Aims are: to optimize the dose level and route of administration in concert with selecting the active enantiomer using well-defined rodent models of ALS; to conduct chemical process development and small to intermediate scale manufacture of compound (drug substance) according to Good Manufacturing Practices (GMP); to conduct appropriate supporting toxicology and pharmacology studies (including gene toxicity and metabolism) according to Good Laboratory Practices; to evaluate in ALS rodent models the utility of C-tau and other molecules as appropriate, as a biomarker for translation into the clinical setting. With a positive preclinical safety and efficacy profile, an IND will be prepared, filed with FDA and Orphan Drug Designation sought. As the compound may exert an effect against the neuroinflammatory component of ALS and many neurological diseases such as Huntington's, Parkinson's and Alzheimer's, EncorePharma will support, as appropriate, experimental studies with the compound and/or other related compounds in models and systems relevant to these diseases. The need to move this potential therapeutic forward for a disease that has very few treatment alternatives cannot be understated. A total of 60,000 to 100,000 individuals are estimated to be affected with ALS worldwide at any given time, and the incidence of the disease is approximately five to nine persons per 100,000. The market potential for a therapeutic hi ALS alone is $100-300 million.