Humanized Kidney Cellular Toxicity Platforms

Principal Investigators for Small Business DiscoveryBioMed Inc DBM
Project Summary Abstract
The over arching goal of this proposed SBIR driven program is to create relevant DiscoveryBioMed DBM
human cellular toxicity HCT platforms for the kidney grown in D and in D cell culture formats for a new
gold standard in lead therapeutic asset and materials in vitro testing and to reduce markedly the need for and
the number of animals used in preclinical testing Primary cultures of different human cell types from renal
tissue will be utilized in these cellular toxicity platforms Renal toxicity has arisen surprisingly late in preclinical
development for several high profile biopharmaceutical drugs and biologics in recent efforts It is apparent that
the current methods and standards for preclinical toxicity testing require improvement Recently DBM
launched a new Online Store and offers D tissue culture TC plastic grown human cell platforms of kidney
lung skin and the vasculature for HCT testing To build upon these initial offerings DBM seeks to design and
establish D cell mono culture and co culture platforms for human kidney cells so as to deepen the creativity
and innovation of our Online Store offerings In addition to preliminary data generated on D cell culture
platforms DBM has begun to establish and optimize D Biogel based culture platforms where normal renal
epithelial cells form tubule like and duct like structures along with spherical fluid filled cysts Moreover DBM
has established D barrier co 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 epithelium Preliminary designs and results will be shared In addition to the
establishment of such D cell culture platforms DBM wishes to test important hypotheses First do any FDA
approved drugs known industry standard drugs or drugs currently in clinical trials display cellular toxicity in
DBM s kidney HCT testing platforms Second does DBM s HCT approach have more value when human cells
are studied in D cell culture formats vs D formats DBM has been hesitant to pursue this line of research
since defined HCT is not yet the gold standard for lead therapeutic asset toxicity testing as mandated by the
FDA or other regulatory agencies It is DBM s view that this needs to change so as to save time resources
and animal lives that are wantonly wasted on a drug or biologic that could be identified early as harmful with
DBM s HCT Our milestones that DBM wishes to meet include to offer existing D HCT testing platforms for
kidney so as to begin to change the culture and methods used to ensure the safety of lead therapeutic assets
to design new D HCT testing platforms for kidney and renal vasculature to optimize and test new D HCT
testing platforms for kidney and renal vasculature versus existing D HCT testing platforms and finally to
explore microfluidics chip based D HCT testing platforms for kidney and renal vasculature
PHS Rev re issued Page Continuation Format PagePrincipal Investigators for Small Business DiscoveryBioMed Inc DBM
Public Health Relevance Statement
DiscoveryBioMed Inc DBM is establishing new paradigms for human cellular toxicity HCT testing so as to
identify harmful lead therapeutics small molecule drugs biologics antibody drug conjugates biosimilars
generic drugs consumer products over the counter formulations personal care products chemicals from the
environment and from consumed goods and materials nanomaterials for drug formulation and delivery etc
at an early stage so as to save the enterprise and marketplace time money and resources in both Randamp D and
regulatory efforts and so as to protect the health of the public Another 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 HCT filter upstream in the process to capture eliminate harmful test assets
This application is focused on the development of human kidney cell based testing platforms in D and D
formats This program is designed as a prelude to entering into a U Cooperative Agreement as part of RFA
ES NIEHS SBIR Phase IIB Awards for Validation and Commercialization of Approaches to Reduce
Animal Use in Toxicology Testing
PHS Rev re issued Page Continuation Format Page