Preclinical Development of a Novel Therapeutic Agent for Idiopathic Pulmonary Fibrosis

特发性肺纤维化（IPF）是一种进行性间质性肺病， 从确诊到现在只有3 - 5年。虽然两种FDA批准的药物，吡非尼酮和尼达尼布， 可能减缓某些IPF患者的肺功能下降速度，两种药物均未显著改变 这种致命疾病的过程。对具有更大功效的新药物存在巨大需求， 用于治疗IPF患者的毒性较小。STTR应用程序解决了未满足的 需要新的治疗IPF的方法，这些方法比 目前的治疗。 小分子肽广泛参与多种细胞事件，在细胞免疫中起着非常重要的作用。 各种细胞功能。对肽作为潜在候选药物的兴趣仍然很高。与 在诸如化学合成和肽制剂、肽药物-特别是 短合成肽和长效肽-在全球市场上迅速增加。的 作为药物的小肽的优点包括它们的高生物活性、高特异性， 低毒性。 FibroBiologics，LLC提出开发新型肽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。在 具体目标1，我们将确定M10在分离的原代肺成纤维细胞中的抗纤维化活性 并评价M10对IPF肺纤维化特征的抑制作用 成纤维细胞在具体目标2中，我们将定义M10在两只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 Tβ R1 CA小鼠模型。这两个具体目标的成功实现将为 关于开发M10作为新型IPF治疗药物的可行性的重要信息， 证明进一步的研究重点是获得FDA批准，规模化生产和人类临床 审判

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.