Material guided drug delivery for pediatric tumors using an implantable biomaterial and bio-orthogonal chemistry

Project Summary Abstract While there are many cancers that are in need of new therapeutic approachespediatric sarcomas are in a class of their ownFive year survival rates in these patients has held steady aroundsincewithout significant improvements in the survival of the remainingof patients since thenA major reason for the lack of progress is the limited size of the marketthere are only aroundnew cancers diagnosed in patients underyears old each year in the U SIn additiondrug development for pediatric patients require additional trials that account for the different anatomy of childrenmetabolismdevelopmental stage and need for pediatric friendly formulations such as liquid instead of tabletsThe end result of these challenges is that out ofnew cancer drugs approved by the FDA betweenandonlyof them a paltryare used in childrenDue to this significant needShasqiIncis focusing this SBIR project on applying its drug delivery technology towards pediatric sarcomasSarcomas are typically treated with chemotherapies like doxorubicinfollowed by surgical resection of the tumorUnfortunatelychemotherapies have severe side effects that can be quite severe and result in deathwhich ultimately limits their use in young patientsOn top of these side effectsdoxorubicin can cause myocardial toxicity that may ultimately lead to fatal congestive heart failureCHFduring therapy or years after termination of therapyas well as secondary AML or myelodysplastic syndromeMDSwhich can also be fatal diseasesThere is clearly a great need to develop chemotherapies and doxorubicin in particular with improved efficacy and improved therapeutic indexwhich would increase the success of tumor resection and increase the survival of pediatric sarcoma patientsTo overcome these adverse events while maintaining efficacyShasqi is developing a patent pending technology that utilizes an implantable biomaterial and prodrugs of chemotherapeuticsShasqi s core technology is based on a bio orthogonalcatch and releasereaction between the biomaterial and the prodrug that results in a localized payload release of the active chemotherapeuticavoiding systemic side effectsThis approach combines the spatial control of injectable biomaterials with the temporal control of systemic drug deliverythus turning systemic drugs into localized medicinesUnder this projectShasqi will tailor its biomaterial and doxorubicin prodrug towards pediatric sarcoma tumors in three mouse studiesA tolerability studya local quantification studyand a xenograft efficacy studyThe resulting data will provide critical data for IND enabling studies as well as inform dosing strategies in expanded efficacy studies in Phase II Project Narrative This project will develop a new therapeutic system to treat pediatric sarcomas with fewer side effects than current chemotherapeuticsThis system will spare the systemic immune system and greatly increase the odds of completely eliminating the cancerous cells and reducing chemotherapy related adverse eventsThe end result will be the first new cancer treatment sincethat increases survival rates in pediatric sarcoma patients