Proprietary drug to treat radiodermatitis

治疗放射性皮炎的专利药物

• 批准号: 10269035
• 负责人: Xiao-Jing Wang
• 金额: $ 52.29万
• 依托单位: ALLANDER BIOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-24 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10269035
• 关键词: Antibodies; Area; Biological Assay; Biotechnology; Breast Cancer Patient; Cancer Patient; Canis familiaris; Cells; Chemistry; Clinical Trials; Complex; Cutaneous; DNA Repair; Data; Dose; Dose-Limiting; Drug Kinetics; Drug Stability; Epithelial; Exhibits; Fibrosis; Formulation; Frequencies; Funding; Guidelines; HIV-1; Human; Inflammation; Inflammatory; Intensity-Modulated Radiotherapy; Investigational Drugs; Investigational New Drug Application; Lead; Length; Malignant Neoplasms; Maximum Tolerated Dose; Measures; Modeling; Modernization; Mus; New Drug Approvals; Oncogenic; Opioid; Pain; Pathogenesis; Pathway interactions; Patients; Peptides; Pharmaceutical Preparations; Pharmacodynamics; Phase; Phase I Clinical Trials; Procedures; Production; Property; Proteins; Quality Control; Radiation; Radiation Dose Unit; Radiation therapy; Radiodermatitis; Rattus; Reference Standards; Regimen; Resistance; Rodent; Safety; Skin; Skin Cancer; Skin Tissue; Smad7 protein; Testing; Therapeutic; Tissues; Topical application; Toxic effect; Toxicokinetics; Toxicology; Transforming Growth Factor beta; Ulcer; absorption; cancer cell; cancer radiation therapy; cancer therapy; chronic wound; cytokine; design; drug candidate; drug efficacy; drug production; good laboratory practice; healing; immunogenic; immunogenicity; keratinocyte; manufacturing scale-up; medication safety; meetings; migration; mouse model; oral mucositis; pharmacodynamic biomarker; pharmacokinetics and pharmacodynamics; pre-clinical; side effect; skin burn; skin damage; skin wound; subcutaneous; systemic toxicity; tat Protein; therapeutic protein

Summary Radiodermatitis is skin tissue damage that occurs in 95% of cancer patients receiving radiotherapy (RT). Although modern RT, e.g., intensity-modulated RT (IMRT) or stereotactic body RT (SBRT), spares more skin areas from RT damage than regular RT, radiodermatitis is still the major toxicity in skin cancer patients treated with SBRT as well as in other cancer patients treated with regular RT where IMRT/SBRT are either unavailable or not suitable, e.g., breast cancer patients. Severe radiodermatitis causes skin erosion, opiate-resistant pain and long-term fibrosis. Current treatments largely aim to ameliorate “skin burn” rather than promoting healing. Allander Biotechnologies, LLC. has developed a proprietary drug to treat radiodermatitis via anti-inflammation, anti-fibrosis, promoting DNA damage repair, and promoting re-epithelialization. To date, we have established a drug production platform, feasibility for efficacy, safety, and pharmacodynamics (PD) markers to develop our drug into a topically applied drug product. In this Phase II application, we will develop Good Manufacturing Practice (GMP)-scalable production and establish reference standards for our drug substance and drug product. We will perform IND (investigational new drug)-enabling PD and pharmacokinetics (PK) studies. We will evaluate potential toxicity of our drug during topical treatment of radiodermatitis in mice and dogs. We will also perform Good Laboratory Practice (GLP) compliant systemic toxicology studies in rodents via intentional systemic delivery of our drug. By the end of Phase II funding, we will have IND data for CMC (Chemistry, Manufacturing and Controls), preclinical PD/PK, potential cutaneous and systemic toxicities in mice and dogs resulted from topical treatment doses, and GLP systemic toxicology in rodents. These data will allow us to design GLP toxicology studies in a larger species, which will be completed with additional funding for IND filing before initiating a Phase I clinical trial.

摘要 放射性皮炎是指95%接受放射治疗的癌症患者的皮肤组织损伤。 尽管现代放射治疗，例如强度调节放射治疗(IMRT)或立体定向体部放射治疗(SBRT)，节省了更多的皮肤 放射性皮炎仍是皮肤癌患者治疗的主要毒副反应 对于接受常规放疗的癌症患者以及常规放疗的癌症患者，在这些患者中，调强放疗/SBRT要么不可用 或不适合，例如，乳腺癌患者。严重的放射性皮炎会导致皮肤侵蚀，抗阿片类药物的疼痛 和长期的纤维化。目前的治疗方法主要是改善“皮肤灼伤”，而不是促进愈合。 Allander BioTechnologies，LLC已经开发出一种专利药物，通过抗炎治疗放射性皮炎， 抗纤维化，促进DNA损伤修复，促进再上皮化。到目前为止，我们已经建立了一个 药物生产平台，有效性、安全性和药效学(PD)标记的可行性，以开发我们的 将药物转化为局部使用的药物产品。在这个第二阶段的应用中，我们将开发Good Manufacturing 实践(GMP)-可规模化生产，并为我们的药品和药品建立参考标准。 我们将进行IND(研究新药)-使PD和药代动力学(PK)研究。我们将评估 我们的药物在小鼠和狗的放射性皮炎局部治疗期间的潜在毒性。我们还将表演 对啮齿动物进行符合GLP规范的系统毒理学研究 把我们的药送到。到第二阶段资助结束时，我们将拥有CMC(化学、制造)的IND数据 和对照)，临床前PD/PK，对小鼠和狗的潜在皮肤和全身毒性 啮齿动物的局部治疗剂量和GLP系统毒理学。这些数据将使我们能够设计GLP 对较大物种的毒理学研究，这将在以下时间之前完成，并为IND备案提供额外资金 启动I期临床试验。