Proprietary biologic treatment to heal skin wounds

治愈皮肤伤口的专有生物治疗

• 批准号: 9788090
• 负责人: Heather Callahan
• 金额: $ 71.5万
• 依托单位: ALLANDER BIOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788090
• 关键词: Acute; Affect; Aging; Animals; Area; Autopsy; Biological; Biological Assay; Biological Response Modifier Therapy; Biotechnology; Blood Circulation; Buffers; Cells; Chronic; Cicatrix; Clinical; Collaborations; Cream; Cutaneous; Data; Development; Diabetes Mellitus; Diabetic mouse; Diabetic wound; Disease; Dose; Drug Kinetics; Elderly; Epidermal Growth Factor; Excipients; Excision; FGF2 gene; Family suidae; Formulation; Funding; Grant; Growth Factor; Guidelines; HIV-1; Health; Healthcare; Human; Hypertrophic Cicatrix; Inflammation; Investigational Drugs; Investigational New Drug Application; Ionic Strengths; Lead; Length; Maximum Tolerated Dose; Measurement; Modeling; Mus; Organ; Patients; Penetration; Peptides; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Phase; Phase I Clinical Trials; Platelet-Derived Growth Factor; Population; Preclinical Testing; Process; Production; Property; Proteins; Protocols documentation; Research Contracts; Rodent; Sampling; Serologic tests; Serum; Signal Transduction; Skin; Skin wound; Solubility; Standardization; Study models; Testing; Texture; Therapeutic Intervention; Tissue Sample; Tissues; Topical application; Toxic effect; Toxicology; Transforming Growth Factor alpha; United States; United States Food and Drug Administration; Variant; Wound Healing; base; cancer risk; care burden; chronic wound; cost; design; diabetic patient; drug development; drug efficacy; efficacy study; good laboratory practice; healing; keratinocyte growth factor; novel; pharmacodynamic biomarker; phase 1 study; phase 2 study; prevent; prototype; response; safety study; scale up; systemic toxicity; tat Protein; wound; wound closure

SUMMARY Chronic skin wounds associated with various diseases (e.g., diabetes) and aberrant healing from acute wounding (e.g., hypertrophic scarring) are a major health care burden. This health burden increases in aging populations. The cost to treat these conditions exceeds $25 billion annually. Currently, REGRANEX®, a cream containing a biologic based on human PDGF (Platelet-Derived Growth Factor), is the only FDA (Food and Drug Administration) approved biologic to treat diabetic wounds. However, the combination of its modest effect on healing and a black box warning added by the FDA for its cancer risk have not translated its drug efficacy to clinical benefit. These facts highlight the sense of urgency for scientific discovery-based therapeutic interventions. Allander Biotechnologies is developing proprietary topically applied biologics to promote wound healing. During the Phase I funding period of this grant, we have tested several biologics and identified our lead biologic to be further developed in this Phase II application. Our Phase I studies revealed that our biologic has multiple functions needed for wound healing. Our Phase II studies will focus on the process of formulation development for our biologic to be used as a topical drug, and data production that will lead us to a successful path for filing an Investigational New Drug (IND) application to the FDA. We will perform pre-formulation studies for solubility as well as stability of physicochemical characterizations and bioactivities of our drug substance. We will use data generated from pre-formulation studies to guide our formulation prototype development. We will produce our biologic at pharmaceutical grade purity and use it as well as the lead formulation(s) to treat diabetic mouse wounds and pig excisional wounds for efficacy studies to define pharmacodynamics (PD) biomarkers and identify potential acute cutaneous/systemic toxicities. By the end of this Phase II funding, we will have stability and physicochemical profiles of our biologic, the lead formulation, PD biomarkers, and protocols (analytical, bioassay, and toxicology) standardized for generating additional IND data under Good Laboratory Practice conditions.

总结 与各种疾病相关的慢性皮肤创伤（例如，糖尿病）和急性 创伤（例如，增生性疤痕）是主要的健康护理负担。这种健康负担随着年龄的增长而增加 人口。治疗这些疾病的费用每年超过250亿美元。目前，REGRANEX®，一种 含有基于人PDGF（血小板衍生生长因子）的生物制品，是FDA（食品和药物管理局）唯一的 药物管理局）批准的生物治疗糖尿病伤口。然而，其温和的效果 FDA为其癌症风险添加的黑框警告并没有将其药物疗效转化为 临床获益。这些事实突出了以科学发现为基础的治疗的紧迫感 干预措施。Allander Biotechnologies正在开发专有的局部应用生物制剂，以促进伤口愈合 治愈在第一阶段的资助期间，我们已经测试了几种生物制剂，并确定了我们的 在第二阶段申请中将进一步开发生物制品。我们的第一阶段研究表明， 具有伤口愈合所需的多种功能。我们的第二阶段研究将集中在制定的过程中， 开发我们的生物制剂作为局部药物，以及数据生产，这将使我们成功地 向FDA提交研究性新药（IND）申请的途径。我们将进行预配制 本品的溶解性、理化性质和生物活性的稳定性研究 实质内容。我们将使用配方前研究产生的数据来指导我们的配方原型 发展我们将生产医药级纯度的生物制品，并将其与铅一起使用 用于治疗糖尿病小鼠伤口和猪切除伤口的有效性研究的制剂， 药效学（PD）生物标志物，并确定潜在的急性皮肤/全身毒性。年底前 在第二阶段的资金支持下，我们将获得我们的生物制剂，主要制剂， PD生物标志物和标准化方案（分析、生物测定和毒理学），用于生成额外IND 数据符合药物非临床研究质量管理规范条件。