Preclinical Development of a Novel Therapeutic Agent for Idiopathic Pulmonary Fibrosis

特发性肺纤维化新型治疗剂的临床前开发

基本信息

批准号：
10696538
负责人：
GALINA S BOGATKEVICH
金额：
$ 29.93万
依托单位：
FIBROBIOLOGICS, LLC
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：
2023-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10696538
关键词：
Address Affect Alveolar Amino Acids Animal Model Anti-Inflammatory Agents Apoptosis Architecture Biological Biological Models Biological Response Modifier Therapy Biotechnology Bleomycin Bronchoalveolar Lavage Fluid C-terminal Cell Aging Cell Culture Techniques Cell physiology Characteristics Chronic Cicatrix Clinical Trials Collaborations Collagen Data Deposition Development Diagnosis Disease Dose Down-Regulation Epithelial Cells Evaluation Event Exhibits Extracellular Matrix Extracellular Matrix Degradation Extracellular Matrix Proteins FDA approved Fibroblasts Fibrosis Formulation Goals Human In Vitro Inflammation Interstitial Lung Diseases Lead Legal patent Lung Lung diseases MET gene Marketing Measurement Modeling Mus Myofibroblast Pathologic Patients Peptides Persons Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Phenotype Physiology Pirfenidone Plasma Play Pre-Clinical Model Preventive Process Production Property Proteins Public Health Pulmonary Fibrosis Quantitative Evaluations Receptor Protein-Tyrosine Kinases Role Small Business Technology Transfer Research Specificity Structure of parenchyma of lung TGF-beta type I receptor Therapeutic Therapeutic Agents Toxic effect Treatment-related toxicity United States Work aged alveolar epithelium chemical synthesis cytokine drug candidate efficacy validation fibrogenesis good laboratory practice idiopathic pulmonary fibrosis improved interest mortality mouse model nintedanib novel novel strategies novel therapeutic intervention novel therapeutics patient retention peptide drug pharmacologic preclinical development preclinical evaluation primary endpoint pulmonary function pulmonary function decline receptor screening secondary endpoint senescence success treatment strategy

项目摘要

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a median survival of only 3 - 5 years from diagnosis. Although two FDA-approved drugs, pirfenidone and nintedanib, may slow the rate of decline of lung function in some IPF patients, neither drug significantly alters the course of this lethal disease. There is a great need for new drugs with greater efficacy and less toxicity for the treatment of patients with IPF. This STTR application addresses the unmet need for new therapeutic approaches to IPF that would be more effective and less toxic than current treatments. Small peptides are widely involved in multiple cellular events and play very important roles in various cell functions. Interest in peptides as potential drug candidates remains high. With advances in such fields as chemical synthesis and peptide formulation, peptide drugs - especially short synthetic and long-acting peptides - are quickly increasing in the global market. The advantages of small peptides as drugs include their high biological activity, high specificity, and low toxicity. FibroBiologics, LLC proposes to develop the novel peptide M10 as an efficacious antifibrotic therapeutic agent, with a lead indication for the treatment of patients who suffer from IPF. In Specific Aim 1, we will determine antifibrotic activity of M10 in primary lung fibroblasts isolated from IPF patients and evaluate an inhibitory effect of M10 on fibrogenic characteristics of IPF lung fibroblasts. In Specific Aim 2, we will define the efficacious dosing of M10 in two different animal models of pulmonary fibrosis: bleomycin-induced therapeutic mouse model and FSP-driven TβR1CA mouse model. The successful completion of these two specific aims will provide important information about the feasibility of developing M10 as a novel IPF therapeutic and will justify further studies focusing on gaining FDA clearance, scaling production, and a human clinical trial.

特发性肺纤维化（IPF）是一种进行性间质性肺疾病，中位生存期为尽管吡非尼酮和尼达尼布这两种 FDA 批准的药物，距诊断仅 3 - 5 年。可能会减缓某些 IPF 患者肺功能下降的速度，但这两种药物都不会显着改变这种致命疾病的病程非常需要具有更大功效和更有效的新药物。治疗 IPF 患者的毒性较小该 STTR 应用解决了未满足的问题。需要新的 IPF 治疗方法，该方法比传统方法更有效且毒性更小目前的治疗方法。小肽广泛参与多种细胞事件，在人们对肽作为潜在候选药物的兴趣仍然很高。化学合成和肽制剂、肽药物等领域的进展 - 特别是短合成肽和长效肽 - 在全球市场上迅速增长。小肽作为药物的优点包括生物活性高、特异性高、低毒。 FibroBiologics, LLC 提议开发新型肽 M10 作为有效的抗纤维化药物治疗剂，主要适应症为治疗 IPF 患者。具体目标1，我们将测定分离的原代肺成纤维细胞中M10的抗纤维化活性来自 IPF 患者并评估 M10 对 IPF 肺纤维化特征的抑制作用在具体目标 2 中，我们将确定 M10 在两种不同动物中的有效剂量。肺纤维化模型：博来霉素诱导的治疗性小鼠模型和 FSP 驱动的 TβR1CA小鼠模型的成功完成将提供这两个具体目标。有关开发 M10 作为新型 IPF 治疗药物的可行性的重要信息，并将证明进一步研究的重点是获得 FDA 批准、扩大生产和人体临床审判。