Clinical Development of JS-K for the Treatment of Cancer

PROJECT DESCRIPTIONJSK TherapeuticsJSKTDirect to Phase II Application Nitric oxideNOis a potentially powerful therapy against cancerSpontaneous NO generating drugs cannot be used to treat malignancies because of the pleiotropic effects of NOIn particularNO is a potent vasodilator with resultant hypotensionIn order to make NO based cancer therapy possibleit is necessary to develop agents that deliver NO preferentially to malignant cellsIn collaboration with DrLarry Keefer at the National Cancer InstituteDrPaul Shami has developed such a drug using compounds that release NO upon interaction with glutathioneGSHin a reaction catalyzed by Glutathione S TransferasesGSTThis drug design exploits the over expression of GST in malignant cellsA lead compound was identified as the most active of this familyOdinitrophenylethoxycarbonylpiperazinyl diazeniumdiolateor JSKJS K has potent and broad spectrum anti cancer activity in vitro and in vivoBecause of challenging solubility and stability propertiesthe Shami lab has developed a formulation for JS K using PluronicPmicellesJS K formulated in PmicellesPJS Kwas well tolerated in a non GLP dog toxicology study without the induction of hypotensionJS K is directly cytotoxic to malignant cells and also an inhibitor of angiogenesisJS K is a very efficient consumer of the anti oxidant tripeptide glutathioneGSHrendering malignant cells particularly susceptible to oxidative stressJS K is not toxic towards normal hematopoietic cellsJS K is synergistic with cytarabine against acute myeloid leukemiaAMLand with bortezomib against multiple myelomaMMRecent data suggest that JS K may sensitize MM cells to the cytotoxic effect of natural killerNKcellsraising the possibility of synergistic combinations with novel immunomodulatory agentsOne kilogram of JS K Active Pharmaceutical Ingredient was produced under cGMP conditionsJSK TherapeuticsJSKTwas founded to lead commercialization of JS KThe United States Food and Drug Administration has granted orphan drug designation for JS K for the indications of AML and MMJSKT plans to develop JS K initially for the treatment of AML and MMThe objective of this project is to complete pre clinical animal toxicology studies needed to file an Investigational New DrugINDapplication with the FDAInaimsan analytical method for the measurement of JS K in biologic matrices will be developed and validatedGLP toxicology studies in rats and dogs using a schedule of administration that reproduces the prospective clinical schedule will be conductedGLP lung and central nervous system toxicology studies will be conducted in ratsand a GLP cardiovascular system toxicology study will be conducted in dogsAt the completion of this projectJSKT will submit an IND application to the FDA in order to start Phase I clinical trials for relapsed refractory AML and MMThis will allow partnering with an established pharmaceutical company or obtaining venture investment in order to complete the clinical development and commercialization of JS Kthus adding a potent new drug to our armamentarium aimed at diminishing the pain and suffering associated with cancer