Humanized Kidney Cellular Toxicity Platforms

The over arching goal of this proposed SBIR driven program is to create relevant DiscoveryBioMedDBMhuman cellular toxicityHCTplatforms for the kidney grown inD and inD cell culture formats for a newgold standardin lead therapeutic asset and materials in vitro testing and to reduce markedly the need for and the number of animals used in preclinical testingPrimary cultures of different human cell types from renal tissue will be utilized in these cellular toxicity platformsRenal toxicity has arisen surprisingly late in preclinical development for several high profile biopharmaceutical drugs and biologics in recent effortsIt is apparent that the current methods and standards for preclinical toxicity testing require improvementRecentlyDBM launched a new Online Store and offersD tissue cultureTCplastic grown human cell platforms of kidneylungskin and the vasculature for HCT testingTo build upon these initial offeringsDBM seeks to design and establishD cell mono culture and co culture platforms for human kidney cellsso as to deepen the creativity and innovation of our Online Store offeringsIn addition to preliminary data generated onD cell culture platformsDBM has begun to establish and optimizeD Biogel based culture platforms where normal renal epithelial cells form tubule like and duct like structuresalong with spherical fluid filled cystsMoreoverDBM has establishedDbarrierco culture platforms where polarized human renal epithelial cell monolayers form on permeable filter supports and where vascular endothelial cells or other relevant cell types on grown immediately beneath the epitheliumPreliminary designs and results will be sharedIn addition to the establishment of suchD cell culture platformsDBM wishes to test important hypothesesFirstdo any FDAapproved drugsknown industry standard drugsor drugs currently in clinical trials display cellular toxicity in DBM s kidney HCT testing platformsSeconddoes DBM s HCT approach have more value when human cells are studied inD cell culture formats vsD formatsDBM has been hesitant to pursue this line of research since defined HCT is not yet thegold standardfor lead therapeutic asset toxicity testing as mandated by the FDA or other regulatory agenciesIt is DBM s view that this needs to changeso as to save timeresourcesand animal lives that are wantonly wasted on a drug or biologic that could be identified early as harmful with DBM s HCTOur milestones that DBM wishes to meet includeto offer existingD HCT testing platforms for kidney so as to begin to change the culture and methods used to ensure the safety of lead therapeutic assetsto design newD HCT testing platforms for kidney and renal vasculatureto optimize and test newD HCT testing platforms for kidney and renal vasculature versus existingD HCT testing platformsandfinallyto explore microfluidicschipbasedD HCT testing platforms for kidney and renal vasculature DiscoveryBioMedIncDBMis establishing new paradigms for human cellular toxicityHCTtesting so as to identify harmful lead therapeuticssmall molecule drugsbiologicsantibody drug conjugatesbiosimilarsgeneric drugsconsumer productsover the counter formulationspersonal care productschemicals from the environment and from consumed goodsand materialsnanomaterials for drug formulation and deliveryetcat an early stage so as to save the enterprise and marketplace timemoney and resources in both Randamp D and regulatory efforts and so as to protect the health of the publicAnother important goal is to reduce the number of animals required for preclinical testing and the number of lead assets progressed to this inflection point by having a more relevant in vitro HCTfilterupstream in the process to capture eliminate harmful test assetsThis application is focused on the development of human kidney cell based testing platforms inD andD formatsThis program is designed as a prelude to entering into a UCooperative Agreement as part of RFAESNIEHS SBIR Phase IIB Awards for Validation and Commercialization of Approaches to Reduce Animal Use in Toxicology Testing