SBIR-STTR Award

Lodestone Biomedical’s Immunotherapy Response Indication System (IRIS) interrogates the binding states of functionalized magnetic nanoparticles (fMNPs) localized in biosensor probes for direct in vivo longitudinal monitoring of therapeutic responses in the patient tumor immune microenvironment (TIME). Herein, we propose to commercialize the IRIS platform technology for pharmacotyping immunotherapies and temozolomide (TMZ) in glioblastoma multiforme (GBM) brain tumors. IRIS technology offers the potential for direct in vivo pharmacotyping capable of differentiating phenotypic responses across ultimately numerous tumor-derived oncogenic and immunogenic factors. This Phase 1 project directly validates the IRIS platform device measurements of target binding sensitivity to singleplex fMNP pairs in solution vs standard ELISA via Bland-Altman plot analysis, with a go-no-go requirement for rt95% CI. The potential for IRIS platform technology will be demonstrated across a restricted subset of target specific biosensors in the well- characterized GBM model system, as well as appropriately pharmacotyping responsiveness to TMZ in more diverse MGMT positive and negative patient derived tumor lines. Finally, preliminary investigations of safety and proof of concept will be demonstrated in real time, localized, in vivo GBM pharmacotyping of combination therapy. Ultimately, IRIS technology will bring reliable indicators of therapeutic responsiveness with a practical implementation to the patient bedside.

This project addresses the problem that several rounds of varied immunotherapy treatments over an extended period are often needed to find one that is effective in treating tumors in a particular patient. The proposed solution is an Immunotherapy Response Indication System (IRIS) to monitor treatment response directly in a patient's own tumor while testing sub therapeutic doses of multiple candidate drugs to determine the best therapeutic option rapidly and safely. The intratumoral monitoring capabilities of the proposed IRIS implantable biosensor and wireless magnetic reader are key to enabling this pharmacotyping strategy. The work plan in this Phase II contract focuses on preclinical safety and performance testing that is foundational to future clinical translation. This pharmacotyping capability enabled by IRIS will allow clinicians to optimize treatment decisions in the early stages of treatment, and during the later stages of treatment in cases of acquired resistance. Our initial clinical product development goal is to track real-time responses within the tumor to immunotherapy in glioblastomas and melanoma brain metastases. Enabling faster selection ofpatient-specific treatments could increase cancer survival rates in the future

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