Development of an immunomodulating peptide as a therapy for osteosarcoma in canine and human

骨肉瘤(OSA)是儿童最常见的原发骨恶性肿瘤。 青少年，约占所有儿童肿瘤的5%(www.ancer.gov)。 骨肉瘤主要发生在四肢的长骨，包括最常见的 股骨、胫骨和肱骨1。目前对诊断为人类患者的护理治疗标准 OSA包括多药新辅助化疗(阿霉素+顺铂+/- 甲氨蝶呤)，然后手术切除原发灶和辅助化疗， 治愈了大约60%到70%的患者1-3。然而，高达40%的新诊断患者 表现为局部疾病最终会发展到肺部转移，这表明 许多患者在确诊时或确诊时已有肺部微转移 在围手术期发展。4.先天性巨结肠患儿的5年生存率 转移性OSA非常低，徘徊在20%-30%左右，这一比率在 30多年2.显然，迫切需要新的治疗方法，特别是能够 抑制OSA的转移过程。Pharmain正在开发免疫调节肽 具有独特的抗肿瘤和抗纤维化特性，用于治疗骨肉瘤等 癌症类型。该多肽的抗肿瘤活性已被证明是一种单一疗法， 与其他免疫/化疗药物联合应用于多种癌症模型，包括OSA 转移模型。飞行员毒性数据已经获得，Pharmain建议进行临床 在犬阻塞性睡眠呼吸暂停综合征患者中作为人类和并行产品开发的翻译工具的试验 用于兽医应用。其他建议的工作是为阶段1的人员启用IND 临床试验，包括生产GLP-TOX所需的药物物质和药物产品 和临床研究，完成GLP-TOX研究，并为OSA提交IND 指示。

Osteosarcoma (OSA) is the most common primary malignancy of bone in children and adolescents, accounting for approximately 5% of all childhood tumors (www.cancer.gov). Osteosarcoma occurs primarily in the long bones of the limbs, including most commonly the femur, tibia, and humerus1. The current standard of care therapy for human patients diagnosed with OSA includes multi-agent neoadjuvant chemotherapy (doxorubicin + cisplatin +/- methotrexate) followed by surgical resection of the primary lesion and adjuvant chemotherapy, curing approximately 60 to 70% of patients 1–3. However, up to 40% of newly diagnosed patients presenting with localized disease eventually develop metastases to the lung, indicating that many patients already have micrometastases present in the lung at the time of diagnosis or develop them during the perioperative period 4. The 5-year survival rate for children with metastatic OSA is extremely low, hovering around 20%-30%, a rate that has not improved in over 30 years 2. Clearly, novel therapies are in critical need, specifically molecules capable of inhibiting the process of OSA metastasis. PharmaIN is developing immunomodulating peptide with unique anti-tumor and anti-fibrotic properties for the treatment of osteosarcoma and other cancer types. The peptide’s anti-tumor activity has been demonstrated as a monotherapy and combination with other immuno/chemotherapies in multiple cancer models, including OSA metastatic model. Pilot tox data has been obtained and PharmaIN proposes to conduct a clinical trial in canine OSA patients as a translation tool for human and concurrent product development for veterinary applications. The additional proposed work is IND enabling for a Phase 1 human clinical trial and consists of manufacturing drug substance and drug product needed for GLP-tox and clinical studies, completion of GLP-tox studies and submission of the IND for the OSA indication.