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: 10545317
• 负责人: Jennifer Baltz
• 金额: $ 80.88万
• 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/10545317
• 关键词: 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; Failure; Fibrosis; Funding; Goals; Grant; Half-Life; Health Care Costs; Healthcare; Heart failure; Human; Immunomodulators; Incentives; Incubated; Intellectual Property; Intravenous; Lead; 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; Treatment Failure; Western World; cardioprotection; chemical stability; chemical synthesis; commercial application; commercialization; constriction; coronary fibrosis; drug development; experimental study; extracellular; 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.

项目摘要/摘要 保留的射血分数（HFPEF）是医疗保健的主要驱动因素之一 西方世界的成本，可以说是心脏病学中最大的未满足需求。目前，那里 没有FDA批准的药物可以治疗绝大多数HFPEF患者。 最近，II期pirouette试验表明，免疫调节药物Pirfenidone， 销售用于治疗罕见肺部疾病，对 HFPEF。不幸的是，吡非酮是一种次优的药物。实际上，由于它的贫穷 药代动力学，患者需要每天服用2次大药，并且经常发育 轻度至中度副作用导致剂量减少或终止治疗（38％ 经过治疗的患者必须在Pirouette试验中停止pirfenidone）。而且，来自 商业观点，pirfenidone没有知识产权保护，因此 制药公司没有动力为进一步的应用开发它。 i-cordis具有pegymet的pirfenidone来获得“ Pegydone”，这是一个更好的分子实体 与吡富烯酮相比，暴露，毒性较少和优越的治疗作用。 I-Cordis已经完成 啮齿动物模型中的概念研究证明。在SBIR II期授予I-Cordis请求支持中 完成关键的临床前研究，以在 潜在的投资者。 在完成第二阶段赠款之后，该公司计划筹集稀释资金 通过临床试验，FDA批准和 Pegydone作为治疗HFPEF的处方药的商业化。