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

• 批准号: 10885315
• 负责人: James Blackledge
• 金额: $ 102.54万
• 依托单位: SARYA, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10885315
• 关键词: Development; Commercialization; New; Molecularly; Targeted

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.

项目概要 Sarya LLC（Sarya）是一家核医学技术公司，旨在将放射性药物商业化。 该快速通道 STTR 的目标是开发一种新的特异性显像剂，用于诊断、分期和 治疗血液癌症、多发性骨髓瘤（MM）。 MM 是第二大常见的血液癌症 估计每年有 32,000 例新病例和 13,000 例死亡。准确检测对于增强性能至关重要 MM 患者的生存率。传统的骨骼检查和骨扫描对溶骨性药物的敏感性有限 病变表现为MM。使用 PET 放射性药物进行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，能够准确检测、 对全身的 MM 细胞进行定位和表型分析。 18F-氟脱氧葡萄糖 (FDG) 是唯一获得 FDA 批准的 MM用PET显像剂。不幸的是，MM 细胞表达低水平的 GLUT-1 转运蛋白和己糖激酶， 这是 FDG 吸收和保留所必需的。此外，MM 骨髓中含有 FDG 亲和力 炎症细胞。对分子靶向、敏感和特异性 MM 显像剂的需求尚未得到满足 可以准确对MM进行分期和再分期，识别高危MM患者，指导个性化MM治疗， 并评估治疗的临床反应。 STTR 的产品将是一种特异且敏感的 PET 用于 MM 的显像剂 (64Cu-LLP2A)。已发布的数据和正在进行的首次人体试验结果显着 通报了该提案第一阶段和第二阶段的目标。第一阶段部分包括两个具体目标：(1) 在小鼠中进行剂量递增和单剂量毒性测试。 (2) 编制新剂量数据并提交 FDA 的 eIND 修正案。第一阶段将实现三个里程碑：(1) 将根据 未观察到不良反应水平（NOAEL），即器官毒性的临床症状（载体与实验）。 (2) 基于新测定的质量和体内临床前图像质量数据，新的比活性 (Ci/mol) 将成立。 (3) 获得 FDA 对 Sarya 赞助的修订 eIND 申请的批准。第二阶段 该部分涉及一项临床试验，有一个具体目标：量化 64Cu-LLP2A-PET 成像的功效 在前瞻性成像试验中检测人类活动性 MM。第二阶段的里程碑是：（1）表现出高水平 64Cu-LLP2A 与 FDG 在 MM 中的检出率（局灶性病变阳性扫描的百分比，p<0.05） 患者。 (2) 将使用标准护理骨髓评估 64Cu-LLP2A 对活动性 MM 的准确性 (BM)活检和血清生物标志物M蛋白水平作为参考标准。相关系数为 0.7 将被认为相当强。综上所述，一期将证明64Cu-LLP2A可耐受的可行性 NOAEL 产生新的 eIND。二期工程将提供64Cu-LLP2A-PET初步性能数据 支持 64Cu-LLP2A 作为新分子实体 (NME) 的新药申请，以供 FDA 批准第二阶段 临床试验。