Development of BIO 300 as a novel treatment for idiopathic pulmonary fibrosis

BIO 300 的开发作为特发性肺纤维化的新型治疗方法

• 批准号: 10603367
• 负责人: MICHAEL D KAYTOR
• 金额: $ 29.85万
• 依托单位: HUMANETICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603367
• 关键词: Acceleration; Adoption; Affect; Age; Biological Markers; Biological Models; Bleomycin; Cancer Patient; Chest; Cicatrix; Clinic; Clinical; Clinical Research; Collagen; Combined Modality Therapy; Data; Deposition; Development; Diagnosis; Disease; Disease Progression; Dose; Dose Limiting; Drug Kinetics; Dyspnea; Exhibits; Exposure to; FDA approved; Fatigue; Feedback; Foundations; Future; Gases; Gene Expression; Genistein; Goals; Histopathology; In Vitro; Incidence; Inflammatory; Inflammatory Infiltrate; Ionizing radiation; Life; Lung; Lung Compliance; Lung diseases; Malignant neoplasm of lung; Measures; Mediator; Modeling; Multiple Organ Failure; Mus; Non-Small-Cell Lung Carcinoma; Oral; Outcome; Patients; Persons; Pharmaceutical Preparations; Phase; Pirfenidone; Pre-Clinical Model; Prognosis; Pulmonary Fibrosis; Pulmonary Hypertension; Pulmonary Inflammation; Quality of life; Radiation; Radiation Therapy Oncology Group; Radiation therapy; Reporting; Research; Respiratory Failure; Safety; Serum; Small Business Innovation Research Grant; Suspensions; System; TGF Beta Signaling Pathway; Therapeutic; Time; Tissues; Toxic effect; Translations; Treatment Efficacy; United States; Work; antifibrotic treatment; clinical development; effective therapy; functional disability; healthy volunteer; idiopathic pulmonary fibrosis; improved; in vivo Model; indium-bleomycin; lung injury; meetings; men; mouse model; nano; nanoparticle; next generation; nintedanib; novel; novel therapeutics; patient tolerability; pre-clinical; prevent; pulmonary function; pulmonary function decline; reduce symptoms; research clinical testing; side effect; treatment effect; tumor

Project Summary Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by progressive scarring of the tissue in the lungs. IPF is associated with a particularly poor prognosis with most patients succumbing to the disease within 3-5 years from the time of diagnosis. Two antifibrotic therapies, nintedanib and pirfenidone, have been approved in recent years for the treatment for IPF based on their ability to slow the rate of decline in lung function in patients, however, neither treatment have been shown to lead to meaningful improvements in patient quality of life, and both have issues with patient tolerability. Humanetics is developing BIO 300, a nanosuspension of synthetic genistein, as a therapy to mitigate pulmonary fibrosis resulting from exposure of the lungs to ionizing radiation. Genistein has been shown to exhibit antifibrotic activity in a variety of in vitro and in vivo model systems through its inhibition of proinflammatory and profibrotic gene expression induced by activation of the canonical NF-κB and TGF-β signaling pathways. Based on these findings, we hypothesize that BIO 300 may have significant therapeutic potential as a therapy for IPF patients. Importantly, BIO 300 has demonstrated an exceptional clinical safety profile in clinical studies in both healthy volunteers and lung cancer patients undergoing radiotherapy, which will streamline its path toward future clinical evaluation as an IPF treatment. The goal of this phase 1 SBIR project is to evaluate the utility of BIO 300 as a treatment for IPF by measuring its ability to mitigate pulmonary fibrosis in the bleomycin lung injury mouse model – the preferred model for evaluating candidate IPF therapeutics. Specific Aim 1 is a BIO 300 dose ranging study to determine the therapeutic efficacy of BIO 300 to reduce pulmonary fibrosis and expression of disease-related biomarkers in the bleomycin lung injury mouse model. Specific Aim 2 will assess the impact of combining BIO 300 with each of the currently approved IPF drugs to determine if combination therapy provides an additional treatment benefit. Specific Aim 3 will be to request and conduct a Type C meeting with the FDA to discuss the nonclinical data obtained from the studies completed under the first two Specific Aims, and solicit guidance on future development activities aimed at advancing BIO 300 toward clinical evaluation as an IPF treatment.

项目摘要 特发性肺纤维化（IPF）是一种严重的肺部疾病，其特征是组织进行性疤痕 在肺部。 IPF与预后特别差有关，大多数患者屈服于该疾病 从诊断开始后的3 - 5年内。两种抗纤维化疗法nintedanib和pirfenidone已是 近年来批准了IPF治疗的基于肺功能下降速度的能力 但是，在患者中，两种治疗都没有证明会导致患者质量的有意义改善 生命，两者都有患者耐受性的问题。 人类遗传正在开发Bio 300，一种合成染料木黄酮的纳米悬浮剂，以减轻肺部的疗法 肺暴露于电离辐射引起的纤维化。染料木黄酮已显示出暴露于抗纤维化 通过抑制促炎和纤维化的各种体外和体内模型系统的活性 由规范NF-κB和TGF-β信号通路的激活引起的基因表达。基于这些 调查结果，我们假设生物300可能具有重要的治疗潜力作为IPF患者的治疗。 重要的是，生物300在健康方面表现出了临床研究的出色临床安全性 志愿者和肺癌患者接受放疗，这将简化其通往未来临床的路径 评估作为IPF治疗。 该第1阶段SBIR项目的目标是通过测量Bio 300作为IPF的治疗方法评估Bio 300的实用性 在博来霉素肺损伤小鼠模型中减轻肺纤维化的能力 - 首选模型 评估候选IPF疗法。特定目标1是BIO 300剂量范围研究，以确定 生物300的治疗效率减少肺纤维化和与疾病相关的生物标志物的表达 博来霉素肺损伤小鼠模型。特定目标2将评估将生物300与每个结合的影响 当前已批准的IPF药物中，以确定联合疗法是否提供了额外的治疗益处。 具体目标3将是请求并进行与FDA的C型会议，以讨论非临床数据 从前两个特定目标完成的研究中获得的研究，并征求未来发展的指导 旨在将生物300推进临床评估作为IPF治疗的活动。