SBIR-STTR Award

Direct to Phase II

Significance: Pre-operative embolization (POE) of meningiomas is an established neuroendovascular procedureperformed to reduce the extensive amount of blood loss that occurs during tumor resection. The current practiceis significantly hampered because of efficacy and safety deficiencies of current embolic agents used off-label forthis indication (none of which are designed specifically for POE). Polyvinyl alcohol particles are the most usedembolic agent, but efficacy data raise concerns of their clinical benefit. Trufill and Onyx are liquid-based embolicalternatives but are fraught with limitations of their own. For example, Onyx contains toxic solvent that causespatient pain and discomfort while the technical risks associated with Trufill have negated its wide-spread adoptionin the United States. Thus, there is a need for an easy-to-use, on-label embolic agent designed specifically for POEof meningiomas that provides safe and complete devascularization. Such an embolic would result in faster andsafer surgical resection, representing a significant evolution in the treatment of meningioma patients.Approach: In this Direct to Phase II SBIR, Arsenal Medical will advance its shear-thinning biomaterial technology,a flow responsive embolic (FRE) agent, as a therapy for the POE of meningiomas. For POE to be effective, completedevascularization of the meningioma is desired, which is achieved by total occlusion of all distal vessels that supplythe tumor. Our Phase I results have demonstrated that the FRE exhibits superior distal penetration compared tocommercial liquid embolics, is biocompatible, and can be manually injected through a neurovascularmicrocatheter. The goal of this proposal is to advance the proof-of-concept formulation towards a productconfiguration that is ready for clinical testing via an early feasibility study (EFS), enabling an efficient path tocommercialization. In Aim 1, we will finalize the delivery system and affirm the product's usability with clinicians.Aim 2 will consist of selection of a commercially viable sterilization method, followed by confirmation of productshelf-life. Biocompatibility of the FRE will be confirmed via a pre-clinical study to determine the neurovascularresponse and safety (Aim 3) and ISO10993 biocompatibility testing through biological and chemicalcharacterization assays (Aim 4). The proposed work provides a foundational data set that will be complementedwith post-Phase II activities to advance towards commercialization.Innovation: The FRE biomaterial has adaptive properties enabling it to become a low viscosity fluid under highshear that penetrates and fills the distal vessels supplying the meningioma. As embolization progresses, flow andshear will continually decrease; in response, the FRE progressively increases in viscosity becoming a viscous pastefor controlled injection. The result is complete casting and occlusion of the entire vasculature. Compared to otherliquid embolics, the FRE is less susceptible to incomplete occlusion because its solidification mechanism occursindependent of its microenvironment. Onyx, for example, solidifies via a precipitation effect, forming a hard outershell that can block vessel branch pathways preventing them from deep vessel embolization.

Public Health Relevance Statement:
PROJECT NARRATIVE Despite procedural benefits, the current practice of reducing blood supply to benign brain tumors prior to surgery is not ideal, hampered by the fact that the embolic agents used are limited by their efficacy, safety, and usability. The purpose of this Direct to Phase II SBIR is to advance a novel embolic biomaterial as a new agent. This proposal will lead to a substantial improvement in the standard of care of patients undergoing brain tumor resection and other neurovascular conditions.

Project Terms:
Adoption ; Animals ; Biocompatible Materials ; Biomaterials ; biological material ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Brain ; Brain Nervous System ; Encephalon ; Brain Neoplasms ; Brain Neoplasia ; Brain Tumors ; tumors in the brain ; Communities ; Complement ; Complement Proteins ; Cyanoacrylates ; Therapeutic Embolization ; Embolization Therapy ; Embolotherapy ; embolization ; Ethylene Oxide ; Oxirane ; Evolution ; Exhibits ; Feasibility Studies ; Foundations ; Patient Care ; Patient Care Delivery ; Glues ; Goals ; Grant ; Hemorrhage ; Bleeding ; blood loss ; Human ; Modern Man ; Kidney ; Kidney Urinary System ; renal ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Learning ; Manuals ; meningioma ; Methods ; neurosurgery ; Pain ; Painful ; Paste substance ; Pastes ; Patients ; Physicians ; Polyvinyl Alcohol ; homopolymer Ethenol ; Precipitation ; Radiology Specialty ; General Radiology ; Radiology ; Research ; Risk ; Safety ; Silicones ; Solvents ; Family suidae ; Pigs ; Suidae ; Swine ; porcine ; suid ; Syringes ; Technology ; Testing ; Thinness ; Leanness ; Time ; Toxicology ; United States ; Universities ; Viscosity ; Work ; Device Designs ; Data Set ; Dataset ; base ; Label ; Procedures ; Distal ; Area ; Acute ; Benign ; Clinical ; Penetration ; Phase ; Biological ; Medical ; Chemicals ; Evaluation ; Blood flow ; Reflux ; Neurosurgeon ; neuro-surgeon ; Collaborations ; fluid ; liquid ; Liquid substance ; Life ; programs ; Clinic ; In Situ ; External Carotid Artery Branch ; System ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; biocompatibility ; biomaterial compatibility ; Lytotoxicity ; cytotoxicity ; experience ; human data ; particle ; Performance ; success ; animal data ; professor ; cohort ; Structure ; novel ; Negotiating ; Negotiation ; Mediation ; Prevention ; Reporting ; Abscission ; Extirpation ; Removal ; Surgical Removal ; resection ; Excision ; Property ; response ; blood supply ; vascular supply ; Vascular blood supply ; Effectiveness ; preventing ; prevent ; Data ; in vivo ; research clinical testing ; Clinical Evaluation ; Clinical Testing ; clinical test ; New Agents ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Development ; developmental ; Pathway interactions ; pathway ; preclinical study ; pre-clinical study ; brain tumor resection ; design ; designing ; cost effective ; human study ; Trauma ; innovation ; innovate ; innovative ; pre-clinical research ; preclinical research ; Implant ; usability ; commercialization ; tumor ; standard of care ; risk mitigation ; Sterilization ; Formulation ; neurovascular ; neuro-vascular ; systemic toxicity ; Injections ; first-in-human ; first in man ; secondary endpoint ; secondary end point ; hemocompatibility ; off-label use ; off-label application ; off-label prescribing ;