SBIR CONCEPT AWARD TO NOVOMEDIX- NOVEL SMALL MOLECULES FOR THE TREATMENT OF RHABDOMYOSARCOMA

该产品是一种口服的新型小分子CXCR4抑制剂，用于安全有效地治疗儿童复发或转移性横纹肌肉瘤，目的是提高存活率和长期疗效。 横纹肌肉瘤(RMS)是一种罕见的儿科癌症，在美国每年有300至400例新发病例，其中一半以上发生在10岁以下的儿童。RMS治疗通常包括综合治疗，包括手术、化疗和RT。近20%患有RMS的儿童在确诊时有转移性疾病。转移是治疗失败和死亡的主要原因。尽管采用了多种治疗方案，但转移性RMS的预后很差，5年存活率不到30%，而骨或骨髓转移或转移超过3个部位的患者的存活率为10%。他们的预后几十年来没有改善，迫切需要新的治疗方法来阻止肿瘤的发展，减少这些年轻患者的长期副作用。CXCR4在RMS中高表达，与转移潜能和预后不良相关。NovoMedex已经开发了专利的新型、口服可用小分子文库，并发布了物质组成专利，减少了癌细胞中的CXCR4。这些化合物具有独特的性质组合，在保护心脏的同时靶向肿瘤以及肿瘤微环境。该项目的目标是开发一种新的、更安全、更有效的转移性RMS治疗方法，以延长生命并改善长期结果。

The intended product is an orally available novel small molecule CXCR4 inhibitor for the safe and effective treatment of recurrent or metastatic rhadbomysarcoma in children, with the goal of improving survival rates and long term outcomes. Rhabdomyosarcoma (RMS) is a rare pediatric cancer, with an incidence in the US of 300 to 400 new cases per year, more than half of which are in children less than 10 years old. RMS treatment usually involves a combination of treatments, including surgery, chemotherapy, and RT. Almost 20% of children with RMS have metastatic disease at the time of diagnosis. Metastasis is a major cause of treatment failure and death. Despite heavy multi-modal therapeutic regimens, metastatic RMS has a dismal prognosis, with 5-year survival rates of less than 30% and those with bone or bone marrow metastases or metastases in more than 3 sites have survival rates of <10%. Their prognosis has not improved in decades and novel therapies are desperately needed to halt tumor progression and reduce long term side effects in these young patients. CXCR4 is highly expressed in RMS and correlates with metastatic potential and poor prognosis. NovoMedix has developed proprietary libraries of novel, orally available, small molecules with issued composition of matter patents which reduce CXCR4 in cancer cells. These compounds have a unique combination of properties that target the tumor as well as the tumor microenvironment while protecting the heart. The goal of this project is to develop a novel, safer, more effective treatment for metastatic RMS to extend life and improve long term outcomes.