Proprietary drug to treat radiodermatitis

治疗放射性皮炎的专利药物

基本信息

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
项目类别：
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

项目摘要

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.

概括放射性炎是皮肤组织损伤，在95％接受放射治疗（RT）的癌症患者中发生。虽然现代的RT，例如强度调节的RT（IMRT）或立体定向身体RT（SBRT），但还可以避免更多的皮肤与常规RT相比，RT损伤的区域，放射性炎仍然是治疗的皮肤癌患者的主要毒性与SBRT以及其他常规RT治疗的癌症患者，IMRT/SBRT都无法使用或不合适，例如乳腺癌患者。严重的放射性膜炎会导致皮肤侵蚀，优化耐药性疼痛和长期纤维化。当前的治疗基本上是为了改善“皮肤燃烧”，而不是促进愈合。 Allander Biotechnologies，LLC。已经开发了一种专有药物来通过抗炎治疗放射性炎，抗纤维化，促进DNA损伤修复并促进再上皮化。迄今为止，我们已经建立了药物生产平台，效率，安全性和药效学（PD）标记的可行性以开发我们的药物为局部申请的药物。在此II阶段应用程序中，我们将开发良好的制造业实践（GMP） - 易于生产和建立我们的药物和药物产品的参考标准。我们将执行IND（研究新药）的PD和药代动力学（PK）研究。我们将评估在局部治疗小鼠和狗的放射性膜炎时，我们的药物的潜在毒性。我们也会表演良好的实验室实践（GLP）通过有意的全身性进行啮齿动物中符合啮齿动物的全身毒理学研究输送我们的药物。到第二阶段资金结束时，我们将拥有CMC的IND数据（化学，制造业和对照），临床前PD/PK，小鼠和狗的潜在皮肤和全身毒性。啮齿动物中的局部治疗剂量和GLP全身毒理学。这些数据将使我们能够设计GLP 在较大物种中的毒理学研究，将通过额外的IND提交资金完成启动I期临床试验。