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

项目摘要 特发性肺纤维化（IPF）是一种严重的肺部疾病，其特征在于组织的进行性瘢痕形成 在肺部。IPF与预后特别差相关，大多数患者死于该病 从确诊之日起3-5年内。尼达尼布和吡非尼酮这两种抗纤维化治疗已被 近年来，基于其减缓肺功能下降速度的能力，批准用于治疗IPF 然而，在患者中，两种治疗都没有显示出导致患者质量的有意义的改善。 两者都有患者耐受性的问题。 Humanetics正在开发BIO 300，一种合成染料木黄酮的纳米混悬液，作为减轻肺部疾病的治疗方法。 由于肺部暴露在电离辐射下而导致的纤维化。染料木黄酮已被证明具有抗纤维化 通过抑制促炎和促纤维化， 典型NF-κB和TGF-β信号通路激活诱导的基因表达。基于这些 研究结果，我们假设BIO 300可能具有显著的治疗潜力，作为IPF患者的治疗方法。 重要的是，BIO 300已在两种健康受试者的临床研究中证明了卓越的临床安全性。 志愿者和肺癌患者接受放射治疗，这将简化其未来的临床路径 评估作为IPF治疗。 该SBIR项目的第1阶段目标是通过测量其在治疗IPF中的作用，评估BIO 300作为IPF治疗的效用。 减轻博来霉素肺损伤小鼠模型中肺纤维化的能力-博来霉素肺损伤小鼠模型是 评估候选IPF治疗剂。具体目标1是一项BIO 300剂量范围研究，以确定 BIO 300减少肺纤维化的治疗效果和疾病相关生物标志物的表达 博莱霉素肺损伤小鼠模型。具体目标2将评估将BIO 300与每种 目前获批的IPF药物，以确定联合治疗是否提供额外的治疗获益。 具体目标3是要求与FDA举行C类会议，讨论非临床数据 （a）就首两个特定目的已完成的研究取得的数据，并就未来的发展寻求指引 旨在推进BIO 300作为IPF治疗的临床评价的活动。

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.