BEXION PHARMACEUTICALS, INC. — Department of Health and Human Services SBIR Phase II: 102

Description

DESCRIPTION provided by applicant Our goal is to develop a new molecular entity with a novel mechanism of action for targeting and eliminating glioblastoma multiforme GBM high grade glioma a deadly and invasive brain tumor with no effective treatment Of the patients expected to be diagnosed with GBM this year most will succumb within a year There is an urgent demand for an efficacious anti glioma drug We are developing a new class of therapeutic proteolipid nanovesicle that can target and destroy glioma tumors Composed of the small lysosomal sphingolipid activator protein saposin C SapC aa and the phospholipid dioleoylphosphatidylserine DOPS the stable nm SapC DOPS nanovesicles clinical formulation is called BXQ have unusually high affinity for phosphatidylserine enriched membrane surfaces that occur widely in many types of tumor cells and tumor neovasculature Consistent with sphingolipid activator function BXQ appear to selectively induce tumor cells to undergo ceramide mediated cell death apparently sparing non tumor cells In Phase I of this proposal we demonstrated the feasibility of using SapC DOPS to target and kill intracranial gliomas Intravenous administration of SapC DOPS in mice with orthotopically implanted gliomas resulted in dose dependent improvement in survival In Phase II a GMP compliant formulation of SapC DOPS i e BXQ was developed and potency was confirmed in additional orthotopic preclinical GBM models IND enabling studies are in progress Pharmacokinetics and toxicity studies thus far indicate favorable distribution and safety profiles in rodent and non rodent studies In this three year Phase IIB proposal the key objectives are to file the IND for BXQ complete a Phase clinical trial and prepare for Phase Recognizing that gliomas are highly heterogeneous another objective is to identify and link biochemical factors e g cell surface PS levels genetic markers to the degree of BXQ tumoricidal activity Understanding of these factors will improve dosing strategies and reduce the risk of variable therapeutic response Specific Aims are Scale up GMP production of BXQ File the IND and complete the Phase clinical trial and Correlate susceptibility to killing by BXQ with molecular and cellular characteristics of glioma cell lins from a tumor bank BXQ offers an innovative and potentially powerful approach for slowing tumor growth and eliminating deep seated brain tumors Ultimately we will progress this technology for treating other tumors and for developing tumor targeted imaging diagnostics PUBLIC HEALTH RELEVANCE We are developing a new treatment for glioblastoma multiforme a deadly form of brain tumor that kills over of afflicted patients Current treatment methods consisting of surgery radiation and chemotherapy have not been effective in significantly reducing morbidity Our strategy involves using new proteolipid nanovesicles that can penetrate the tumors and selectively destroy malignant cells without harming normal cells Success in clinical trials will enable us to offer an effective new strategy to treat patients with aggressive brain tumors