Development of a Novel Immunomodulatory Pyridone for the Treatment of Heart Failure with Preserved Ejection Fraction

开发一种新型免疫调节吡啶酮，用于治疗具有保留射血分数的心力衰竭

• 批准号: 10675580
• 负责人: Jennifer Baltz
• 金额: $ 73.99万
• 依托单位: I-CORDIS, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-18 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10675580
• 关键词: Acceleration; Accounting; Affect; American; Biological Availability; Canis familiaris; Cardiology; Clinical Trials; Complex; Data; Development; Disease; Dose; Drug Kinetics; Drug Prescriptions; EFRAC; Exposure to; Eye; FDA approved; Fibrosis; Funding; Goals; Grant; Half-Life; Health Care Costs; Healthcare; Heart failure; Human; Incentives; Incubated; Intellectual Property; Intravenous; Liver Microsomes; Lung diseases; Magnetic Resonance Imaging; Marketing; Measures; Modeling; Molecular; Mus; Myocardial; Myocardial dysfunction; Oral; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Phase; Phase II Clinical Trials; Pirfenidone; Plasma; Prevalence; Process; Production; Prognosis; Property; Pyridones; Rattus; Risk; Rodent Model; Safety; Small Business Innovation Research Grant; Temperature; Therapeutic; Therapeutic Effect; Time; Toxic effect; Toxicology; Western World; aorta constriction; cardioprotection; chemical stability; chemical synthesis; commercial application; commercialization; coronary fibrosis; drug development; experimental study; extracellular; immune modulating agents; immunoregulation; improved; insight; novel; pill; pre-clinical; precision medicine; preclinical study; preservation; prospective; scale up; side effect; small molecule; stability testing

PROJECT SUMMARY/ABSTRACT Heart Failure with preserved Ejection Fraction (HFpEF) is one of the major drivers of healthcare costs in the western world and arguably the largest unmet need in cardiology. Currently, there are no FDA approved drugs to treat the vast majority of patients with HFpEF. Recently, the Phase II PIROUETTE trial showed that the immunomodulatory drug pirfenidone, marketed for the treatment of a rare lung disease, has marked beneficial effects in patients with HFpEF. Unfortunately, pirfenidone is a suboptimal drug. In fact, because of its poor pharmacokinetics, patients need to take 2 large pills three times a day and they often develop mild to moderate side effects that lead to dose reduction or discontinuation of treatment (38% of treated patients had to discontinue pirfenidone in the PIROUETTE trial). Moreover, from a commercial point of view, pirfenidone has no intellectual property protection and therefore pharmaceutical companies have no incentive to develop it for further applications. i-Cordis has PEGylated pirfenidone to obtain “Pegydone”, a new molecular entity with better exposure, less toxicity and superior therapeutic effects than pirfenidone. i-Cordis has completed proof of concept studies in rodent models. In this SBIR Phase II grant i-Cordis requests support to complete critical pre-clinical studies to de-risk its drug development effort in the eyes of potential investors. Following completion of the Phase II grant, the company plans to raise dilutive funding to complete IND filing, and progress through clinical trials, FDA approval and commercialization of Pegydone as a prescription drug for the treatment of HFpEF.

项目总结/摘要 射血分数保留性心力衰竭（HFpEF）是医疗保健的主要驱动因素之一 在西方世界的成本，可以说是最大的未满足的需求，在心脏病学。目前 没有FDA批准的药物来治疗绝大多数HFpEF患者。 最近，II期PIROUETTE试验显示，免疫调节药物吡非尼酮， 用于治疗一种罕见的肺部疾病，对患有以下疾病的患者具有显著的有益效果： HFpEF。不幸的是，吡非尼酮是一种次优药物。事实上，由于其贫穷 药代动力学，患者需要每天三次服用2粒大药丸，并且通常会出现 轻度至中度副作用，导致剂量减少或停止治疗（38%的 在PIROUETTE试验中，接受治疗的患者不得不停用吡非尼酮）。而且从 从商业角度来看，吡非尼酮没有知识产权保护，因此 制药公司没有动力开发它用于进一步的应用。 i-Cordis将吡非尼酮聚乙二醇化，以获得“聚乙二醇酮”，这是一种新的分子实体， 与吡非尼酮相比，暴露量小，毒性小，治疗效果上级。i-Cordis已完成 啮齿动物模型中的概念验证研究。在此SBIR第二阶段授予i-Cordis请求支持 完成关键的临床前研究，以降低其药物开发工作的风险， 潜在投资者。 在第二阶段赠款完成后，该公司计划筹集稀释性资金， 完成IND申请，并通过临床试验，FDA批准和 聚乙二醇酮作为治疗HFpEF的处方药的商业化。