Assessment of chronic toxicity to support the use of topical pirenzepine for treating diabetic neuropathy

Period of Performance: 07/01/2017 - 06/30/2018

$970K

Phase SBIR

Recipient Firm

Winsantor, Inc.
San Diego, CA 92111
Principal Investigator

Abstract

PROJECT SUMMARY The objective of this SBIR Commercialization Readiness Program (CRP) project is to evaluate chronic toxicity of a new therapeutic for diabetic neuropathy in support of an IND submission. Of the 25 million Americans who suffer from diabetes, approximately 50% will be diagnosed with neuropathy, which is characterized by nerve degeneration. Despite the high prevalence of the disease, there is currently no FDA-approved treatment to either prevent diabetes-induced nerve degeneration or promote nerve regeneration. Thus, there is a substantial unmet need to develop more effective treatments for diabetic neuropathy. The founders of WinSanTor have identified a promising candidate which both prevents and reverses neuropathy in rodent models of the disease. The candidate molecule, pirenzepine, was identified using a novel screening methodology developed in the labs of the company?s founders. Pirenzepine has subsequently been evaluated in over a dozen in vivo tests, and has demonstrated the unique ability to ameliorate both epidermal fiber loss and thermal hypoalgesia. Pirenzepine is an approved drug for other indications in non-US countries, and so it is substantially de-risked as a drug development candidate. In a SBIR Fast-track program, WinSanTor successfully executed an expedited pre-clinical program that included: 1) development and validation of bioanalytical methods; 2) pharmacokinetic analyses; 3) optimization of formulation to enhance delivery; 4) generation of a safety profile; and 5) GMP manufacturing of pirenzepine. These efforts fully support the continued execution of the pre-clinical program through the evaluation of chronic toxicity assessments. The focus of this CRP program will be to evaluate the toxicity of pirenzepine when applied topically for 9 months. A 9-month study was chosen to fulfill the 9-month chronic toxicity study requirement for an NDA submission and to support the duration of the anticipated Phase 2 clinical trial protocol that will involve administration for at least 5 months. This study will be executed in mini-pigs and will use a number of toxicity end points, such as mortality observations, clinical observations, Draize scoring, clinical pathology, and histopathology, to fully define a toxicological profile of pirenzepine. The metric of success for this Aim is to achieve to achieve a NOAEL at an exposure level such that there is up to a 10x safety margin for human studies. The completion of this study is critical to an IND submission to the FDA to support subsequent clinical trials.