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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要特发性肺纤维化（IPF）是一种严重的肺部疾病，其特征是组织进行性疤痕形成 IPF 与特别不良的预后相关，大多数患者死于该病。诊断后 3-5 年内，已使用两种抗纤维化疗法：尼达尼布和吡非尼酮。近年来因其减缓肺功能下降速度的能力而被批准用于 IPF 的治疗然而，在患者中，这两种治疗均未显示出对患者质量产生有意义的改善生活，两者都存在患者耐受性的问题。 Humanetics 是 BIO 300，一种合成金雀异黄酮的纳米混悬液，可作为开发肺部疾病的疗法因肺部暴露于电离辐射而导致的纤维化已被证明具有抗纤维化作用。通过抑制促炎和促纤维化，在多种体外和体内模型系统中发挥活性经典 NF-κB 和 TGF-β 信号通路激活诱导的基因表达。研究结果显示，我们认为 BIO 300 作为 IPF 患者的治疗方法可能具有显着的治疗潜力。重要的是，BIO 300 在健康和健康的临床研究中表现出了卓越的临床安全性。志愿者和接受放射治疗的肺癌患者，这将简化其未来临床之路作为 IPF 治疗的评估。该 SBIR 项目 1 期的目标是通过测量 BIO 300 治疗 IPF 的效用来评估 BIO 300 的效用。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 疗法的具体目标 1 是一项 BIO 300 剂量范围研究，以确定 BIO 300 减少肺纤维化和疾病相关生物标志物表达的治疗功效博来霉素肺损伤小鼠模型将评估 BIO 300 与每种药物组合的影响。目前批准的 IPF 药物，以确定联合治疗是否能提供额外的治疗益处。具体目标 3 是要求 FDA 召开 C 类会议，讨论非临床数据从前两个具体目标下完成的研究中获得的结果，并征求对未来发展的指导旨在推进 BIO 300 作为 IPF 治疗的临床评估的活动。