While there are many cancers that are in need of new therapeutic approaches, pediatric sarcomas are in a class of their own. Five-year survival rates in these patients has held steady around 67% since 1990, without significant improvements in the survival of the remaining 1/3 of patients since then. A major reason for the lack of progress is the limited size of the market; there are only around 12,400 new cancers diagnosed in patients under 21 years old each year in the U.S. In addition, drug development for pediatric patients require additional trials that account for the different anatomy of children, metabolism, developmental stage and need for pediatric-friendly formulations?such as liquid instead of tablets. The end result of these challenges is that out of 120 new cancer drugs approved by the FDA between 1948 and 2002, only 30 of them?a paltry 25%?are used in children. Due to this significant need, Shasqi, Inc. is focusing this SBIR project on applying its drug delivery technology towards pediatric sarcomas. Sarcomas are typically treated with chemotherapies like doxorubicin, followed by surgical resection of the tumor. Unfortunately, chemotherapies have severe side effects that can be quite severe and result in death, which ultimately limits their use in young patients. On top of these side effects, doxorubicin can cause myocardial toxicity that may ultimately lead to fatal congestive heart failure (CHF) during therapy or years after termination of therapy, as well as secondary AML or myelodysplastic syndrome (MDS), which can also be fatal diseases. There is clearly a great need to develop chemotherapies?and doxorubicin in particular?with improved efficacy and improved therapeutic index, which would increase the success of tumor resection and increase the survival of pediatric sarcoma patients. To overcome these adverse events while maintaining efficacy, Shasqi is developing a patent-pending technology that utilizes an implantable biomaterial and prodrugs of chemotherapeutics. Shasqi?s core technology is based on a bio-orthogonal ?catch and release? reaction between the biomaterial and the prodrug that results in a localized payload release of the active chemotherapeutic, avoiding systemic side effects. This approach combines the spatial control of injectable biomaterials with the temporal control of systemic drug delivery, thus turning systemic drugs into localized medicines. Under this project, Shasqi will tailor its biomaterial and doxorubicin prodrug towards pediatric sarcoma tumors in three mouse studies: A tolerability study, a local quantification study, and a xenograft efficacy study. The resulting data will provide critical data for IND-enabling studies as well as inform dosing strategies in expanded efficacy studies in Phase II.
This project will develop a new therapeutic system to treat pediatric sarcomas with fewer side effects than current chemotherapeutics. This system will spare the systemic immune system and greatly increase the odds of completely eliminating the cancerous cells and reducing chemotherapy-related adverse events. The end result will be the first new cancer treatment since 1990 that increases survival rates in pediatric sarcoma patients.
