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.
