Topical proprietary biologic to treat oral mucositis

总结 口腔粘膜炎是一种严重的口腔溃疡，是放射或化学放射治疗的常见毒性作用， 使用最大剂量的辐射进行有效的癌症治疗的因素。至少40%，最多70%， 用标准化疗方案或上半身放射治疗的癌症患者发展为口腔粘膜炎。 调强放射治疗（IMRT）可以减轻慢性副作用，但不能减轻口腔粘膜的急性毒性。的 一种新的立体定向体放射治疗（SBRT），将放射治疗引导到肿瘤块，应该可以减少口腔粘膜炎，但这将 不适用于需要化疗、靶向治疗或常规RT的患者。免疫疗法 获得癌症治疗的势头，但口腔粘膜炎似乎更经常发生与免疫治疗。到 迄今为止，Palifermin是一种来源于角质细胞生长因子的蛋白质，是唯一被批准的靶向治疗药物。 美国食品药品监督管理局（FDA）用于预防造血系统恶性肿瘤患者的口腔粘膜炎 其次是骨髓移植（4%的高危人群），但它对现有的粘膜炎没有影响。 Allander Biotechnologies开发了一种专有生物制剂，具有预防和治疗效果 对小鼠局部应用于口腔粘膜后辐射诱导的口腔粘膜炎的影响。我们的生物体拥有 口腔粘膜炎愈合所需的多种功能。在第一期资助期内，我们已 开发了生物生产系统，并证明用这种生物制剂治疗小鼠可以减轻 放射治疗诱导的口腔粘膜炎，但不损害其杀死邻近的口腔癌。在第二阶段 应用，我们将建立生产我们的生物制剂的放大工艺和质量控制。我们将 生成疗效数据以优化药效学（PD）生物标志物。我们会产生初步毒性 设计新药申报所需的药代动力学（PK）和毒理学研究的数据 (IND)应用程序.到第二阶段资金结束时，我们将建立我们的制造程序， 生物学和方案（分析、生物测定、PK和毒理学），准备根据 药物非临床研究质量管理规范（GLP）条件。

Summary Oral mucositis, a severe oral ulceration, is a common toxic effect of radio- or chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. At least 40%, and up to 70%, of cancer patients treated with standard chemotherapy regimens or upper-body radiation develop oral mucositis. Intensity modulated RT (IMRT) lessens chronic side effects, but not the acute toxicity seen in oral mucosa. The new Stereotactic Body RT (SBRT) that directs RT to the tumor mass should reduce oral mucositis, but this will not apply to patients who need chemotherapies, targeted therapies, or conventional RT. The immunotherapy is gaining momentum for cancer therapy, but oral mucositis appears to occur more often with immunotherapy. To date, Palifermin, a protein derived from keratinocyte growth factor, is the only targeted therapy approved by the Food and Drug Administration (FDA) for preventing oral mucositis in patients with hematopoietic malignancy followed by bone marrow transplant (4% of the at-risk population), but it has no effect on existing mucositis. Allander Biotechnologies has developed a proprietary biologic that shows prophylactic and therapeutic effects on radiation-induced oral mucositis in mice upon topical application to oral mucosa. Our biologic possesses multiple functions needed for oral mucositis healing. In the Phase I funding period of this grant, we have developed the biologic production system and demonstrated that treating mice with this biologic alleviated radiotherapy-induced oral mucositis but did not compromise its killing of adjacent oral cancer. In this Phase II application, we will establish the scale-up process and quality controls for manufacturing our biologic. We will generate efficacy data to optimize pharmacodynamics (PD) biomarkers. We will generate preliminary toxicity data to design pharmacokinetics (PK) and toxicology studies required for filing an Investigational New Drug (IND) application. By the end of Phase II funding, we will have established manufacturing procedures for our biologic and protocols (analytical, bioassay, PK and toxicology) ready for generating additional IND data under Good Laboratory Practice (GLP) conditions.