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)是一种以组织进行性疤痕为特征的严重肺部疾病。 在肺里。特发性肺纤维化与预后特别差有关，大多数患者死于这种疾病。 自确诊之日起3-5年内。两种抗纤维化疗法，奈替达尼和吡非尼酮，已经被 近年来批准用于IPF的治疗，基于其减缓肺功能下降的速度的能力 然而，在患者中，这两种治疗都没有显示出对患者质量的有意义的改善。 两者都有患者耐受性的问题。 人类医学正在开发BIO 300，一种合成金雀异黄素的纳米悬浮剂，作为一种缓解肺部疾病的疗法。 肺暴露在电离辐射下引起的纤维化。金雀异黄素已被证明具有抗纤维化作用 通过抑制促炎症和促纤维化在多种体外和体内模型系统中的活性 转录因子-转化生长因子B和转化生长因子-κ-β信号通路激活诱导基因表达。基于这些 根据研究结果，我们假设BIO 300可能具有显著的治疗IPF患者的潜力。 重要的是，BIO 300在临床研究中显示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，这将简化其通往未来临床的道路 作为IPF治疗的评估。 这个第一阶段SBIR项目的目标是评估BIO 300作为治疗IPF的有效性，通过测量其 博莱霉素肺损伤小鼠模型减轻肺纤维化的能力 评估候选IPF疗法。具体目标1是一项BIO 300剂量范围研究，以确定 BIO 300减轻大鼠肺纤维化及相关生物标记物表达的疗效 博莱霉素肺损伤小鼠模型。具体目标2将评估将BIO 300与每个 目前批准的IPF药物，以确定联合治疗是否提供额外的治疗益处。 具体目标3将是要求并与FDA举行一次C型会议，讨论非临床数据 从前两个具体目标下完成的研究中获得，并征求对未来发展的指导 旨在推动BIO 300作为IPF治疗的临床评估的活动。