"Targeted Ac-225-radiopharmaceutical for metastatic uveal melanoma"Period of Performance: 9/18/2017 - 9/17/2019

“针对转移性葡萄膜黑色素瘤的靶向Ac-​​225放射性药物”执行期间：2017年9月18日 - 2019年9月17日

• 批准号: 9576556
• 负责人: RIKKI WATERHOUSE
• 金额: $ 200万
• 依托单位: MODULATION THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2019-09-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9576556
• 关键词: Affinity; Animal Model; Binding; Biodistribution; Blood; Clinical Trials; Contracts; Cutaneous Melanoma; Funding; Human; Ligands; Melanocortin 1 Receptor; Melanoma Cell; Metastatic Melanoma; Organ; Pathology; Performance; Phase; Phase I Clinical Trials; Radiopharmaceuticals; Rare Diseases; Risk; Small Business Innovation Research Grant; Specificity; Tissues; Toxic effect; Uveal Melanoma; commercialization; dosage; drug candidate; drug development; tumor

Melanocortin 1 receptor (MC1R) is highly expressed on uveal and cutaneous melanoma cells and not on any tissues that are of concern for causing toxicity. We developed a proprietary ligand (MC1RL) that binds to melanoma cells with high affinity and specificity. Our recently completed SBIR Phase I contract results show no overt toxicity at dosages of Ac-225-DOTA-Ahx-MC1RL that produce outstanding efficacy against uveal and cutaneous melanoma in animal models. Biodistribution, radiodosimetry, and PK studies also show rapid blood clearance with predominant distribution to the targeted tumor or to clearance organs with no organ specific pathology. These results are very supportive of possible commercialization of a human drug candidate for the treatment of metastatic melanoma.

黑皮质素 1 受体 (MC1R) 在葡萄膜和皮肤黑色素瘤细胞上高度表达，而不是在任何可能引起毒性的组织上表达。我们开发了一种专有配体 (MC1RL)，它以高亲和力和特异性与黑色素瘤细胞结合。我们最近完成的 SBIR I 期合同结果显示，Ac-225-DOTA-Ahx-MC1RL 的剂量没有明显的毒性，在动物模型中对葡萄膜和皮肤黑色素瘤产生了出色的疗效。生物分布、放射剂量测定和药代动力学研究也显示快速血液清除，主要分布到目标肿瘤或没有器官特异性病理的清除器官。这些结果非常支持用于治疗转移性黑色素瘤的人类候选药物的商业化。