SBIR PHASE I - TOPIC 405 - PROJECT TITLE: IN VIVO PHARMACOTYPING OF COMBINATION THERAPY IN PRIMARY BRAIN TUMORSFIRM FIXED PRICE - POP: 09/16/2020 - 0

Lodestone Biomedical的免疫治疗反应指示系统（IRIS）询问位于生物传感器探针中的功能化磁性纳米颗粒（fMNP）的结合状态，以直接在体内纵向监测患者肿瘤免疫微环境（TIME）中的治疗反应。在此，我们建议将IRIS平台技术商业化，用于多形性胶质母细胞瘤（GBM）脑肿瘤中的免疫疗法和替莫唑胺（TMZ）的药物分型。IRIS技术提供了直接体内药物分型的潜力，能够区分最终许多肿瘤源性致癌和免疫原性因子的表型反应。该I期项目通过Bland-Altman图分析直接验证了IRIS平台装置对溶液中的单重fMNP对的靶标结合灵敏度测量与标准ELISA的比较，通过-不通过要求>95% CI。IRIS平台技术的潜力将在充分表征的GBM模型系统中的靶标特异性生物传感器的有限子集中得到证明，以及在更多样化的MGMT阳性和阴性患者衍生肿瘤系中对TMZ的适当药物分型反应性。最后，安全性和概念验证的初步研究将在联合治疗的真实的时间、局部、体内GBM药效分型中得到证实。最终，IRIS技术将带来可靠的治疗反应指标，并在患者床边进行实际实施。

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 >95% 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.