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Development and Commercialization of a New Molecularly Targeted Imaging Agent for Multiple Myeloma

新型多发性骨髓瘤分子靶向成像剂的开发和商业化

基本信息

批准号：
10451065
负责人：
Monica Shokeen
金额：
$ 12.53万
依托单位：
SARYA, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-19 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10451065
关键词：
Administrative Supplement Advanced Development Affect African Age Amendment Anatomy Biological Markers Bone Marrow Bone Marrow Transplantation Bone marrow biopsy Cell Surface Proteins Cells Cessation of life Characteristics Clinical Clinical Trials Complex Data Detection Development Diagnosis Diffuse Discipline of Nuclear Medicine Disease Disease remission Dose Drug Kinetics Elderly Etiology Evaluation FDA approved Family history of Functional Imaging Goals Hematologic Neoplasms Hematopoietic Neoplasms Human Image Imaging technology Immune Incidence Infiltration Inflammatory Injections Integrin alpha4beta1 Lesion Lytic Metastatic Lesion Malignant - descriptor Malignant lymphoid neoplasm Methodology Molecular Molecular Target Multiple Myeloma Mus No-Observed-Adverse-Effect Level Organ Pathogenesis Patients Performance Pharmacology Phase Phase II Clinical Trials Phenotype Plasma Cell Neoplasm Plasma Cells Positron-Emission Tomography Publishing Radiopharmaceuticals Reference Standards Residual Neoplasm Risk Factors SLC2A1 gene Scanning Serum Signal Transduction Skeletal Survey Skeletal bone Small Business Technology Transfer Research Specificity Staging Technology Time Toxic effect Toxicity Tests Tracer Transplantation base bone bone imaging burden of illness clinical imaging clinical translation commercialization efficacy validation first-in-human fluorodeoxyglucose hexokinase high risk imaging agent imaging approach in vivo male mouse model multiple myeloma M Protein novel therapeutics overexpression preclinical imaging prospective sex standard of care success technology development treatment response tumor growth uptake

项目摘要

PROJECT SUMMARY Sarya LLC (Sarya) is a nuclear medicine technology company formed to commercialize radiopharmaceuticals. The goal of this Fast-Track STTR is to develop a new specific imaging agent for diagnosis, staging, and treatment of the hematological cancer, multiple myeloma (MM). MM is the 2nd most common blood cancer with an estimated 32,000 new cases and 13,000 deaths per year. Accurate detection is critical for enhancing survival in MM patients. Traditional skeletal survey and bone scans have sensitivity limitations for osteolytic lesions manifested in MM. Positron Emission Tomography (PET) performed with a PET radiopharmaceutical (imaging agent) is a sensitive, quantitative and non-invasive clinical imaging technology to accurately detect, localize and phenotype MM cells throughout the body. 18F-fluorodeoxyglucose (FDG) is the only FDA- approved PET imaging agent for MM. Unfortunately, MM cells express low levels of GLUT-1 transporter and hexokinase, which are required for FDG uptake and retention. Additionally, MM bone marrow harbors FDG- avid inflammatory cells. There is an unmet need for molecularly targeted, sensitive and specific MM imaging agents that can accurately stage and restage MM, identify high-risk MM patients, guide personalized MM treatment, and evaluate clinical response to treatment. The product of this STTR will be a specific and sensitive PET imaging agent (64Cu-LLP2A) for MM. Published data and ongoing first-in-human trial results have significantly informed the Phase I and II aims of this proposal. The Phase I Segment consists of two specific aims: (1) Perform dose escalation and single dose toxicity testing in mice. (2) Compile data for new dose and submit amendment of eIND to FDA. Three milestones will be met in Phase I: (1) A new mass will be selected based on no-observed-adverse-effect level (NOAEL), i.e. clinical signs of organ toxicity (vehicle vs experimental). (2) Based on the new determined mass, and in vivo preclinical image quality data, a new specific activity (Ci/mol) will be established. (3) Obtain FDA approval of Sarya sponsored amended eIND application. The Phase II segment involves a clinical trial and has one specific aim: Quantify the efficacy of 64Cu-LLP2A-PET imaging for detecting active MM in humans in a prospective imaging trial. Phase II milestones are: (1) Demonstrate high detection rates (% of scans that are positive for a focal lesion, p<0.05) for 64Cu-LLP2A versus FDG in MM patients. (2) Accuracy of 64Cu-LLP2A for active MM will be assessed using standard-of-care bone marrow (BM) biopsies and serum biomarker M-protein levels as the standards of reference. A correlation coefficient of 0.7 will be considered reasonably strong. In summary, Phase I will prove feasibility that 64Cu-LLP2A is tolerable with NOAEL resulting in a new eIND. Phase II will provide 64Cu- LLP2A-PET preliminary performance data to support a New Drug Application for 64Cu-LLP2A as a New Molecular Entity (NME) for FDA approval of Phase 2 clinical trials.

项目摘要 Sarya LLC（Sarya）是一家核医学技术公司，旨在将放射性药物商业化。这个快速通道STTR的目标是开发一种新的特异性成像剂，用于诊断、分期和治疗。治疗血液癌症，多发性骨髓瘤（MM）。MM是第二大最常见的血癌估计每年有32，000例新病例和13，000例死亡。准确检测对于增强 MM患者的生存率。传统的骨骼调查和骨扫描对溶骨性关节炎的敏感性有限。 MM中出现的病变。使用PET放射性药物进行的正电子发射断层扫描（PET）（显像剂）是一种灵敏、定量、无创的临床影像技术，在全身定位和表型MM细胞。18F-氟脱氧葡萄糖（FDG）是唯一的FDA- 不幸的是，MM细胞表达低水平的GLUT-1转运蛋白，己糖激酶，其是FDG摄取和保留所需的。此外，MM骨髓含有FDG- 活跃的炎症细胞对分子靶向、敏感和特异性MM成像的需求尚未得到满足可以准确分期和再分期MM的药物，识别高危MM患者，指导个性化MM 治疗，并评估对治疗的临床反应。该STTR的产品将是一种特定的，敏感的PET显像剂（64 Cu-LLP 2A）用于MM。已发表的数据和正在进行的首次人体试验结果这是该计划第一阶段和第二阶段的主要目标。第一阶段包括两个具体目的：（1）在小鼠中进行剂量递增和单次给药毒性试验。(2)为新的给药并向FDA提交eIND修正案。第一阶段将达到三个里程碑：（1）将建立一个新的质量体系，基于无明显不良作用水平（NOAEL），即器官毒性的临床体征（溶剂与实验性的）。(2)基于新确定的质量和体内临床前图像质量数据，将确定比活度（Ci/mol）。(3)获得FDA批准Sarya申办的修订版eIND 应用程序. II期部分涉及临床试验，并有一个特定的目标：量化的疗效 64 Cu-LLP 2A-PET成像用于在前瞻性成像试验中检测人类活动性MM。二期里程碑是：（1）显示高检出率（局灶性病变阳性扫描的%，p<0.05） MM患者中64 Cu-LLP 2A与FDG的比较。(2)将评估64 Cu-LLP 2A用于活动性MM的准确度使用标准护理骨髓（BM）活组织检查和血清生物标志物M蛋白水平作为标准，参考0.7的相关系数将被认为相当强。总之，第一阶段将证明 64 Cu-LLP 2A在NOAEL下可耐受的可行性，导致新的eIND。第二阶段将提供64 Cu- LLP 2A-PET初步性能数据支持64 Cu-LLP 2A作为新药申请分子实体（NME）用于FDA批准的2期临床试验。