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

项目摘要/摘要 心力衰竭伴保留射血分数(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得到满足的需求。目前，有 FDA没有批准的药物来治疗绝大多数HFpEF患者。 最近，二期旋转试验显示，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有显著的益处 HFpEF。不幸的是，吡非尼酮是一种次优药物。事实上，因为它的贫穷 药代动力学，患者需要一天三次服用两大片药，他们经常会出现 导致剂量减少或停止治疗的轻微至中度副作用(38% 在旋转试验中，接受治疗的患者不得不停止使用吡非尼酮)。此外，从一个 从商业角度来看，吡非尼酮没有知识产权保护，因此 制药公司没有动力将其开发用于进一步的应用。 I-Cordis将吡非尼酮进行聚乙二醇化，得到了一种新的分子实体--佩吉酮，它具有更好的 暴露，毒性小，疗效优于吡非尼酮。I-Cordis已经完成 啮齿动物模型的概念验证研究。在此SBIR第二阶段赠款I--Cordis请求支持 完成关键的临床前研究，以降低其药物开发努力的风险 潜在投资者。 在第二阶段拨款完成后，公司计划筹集摊薄资金至 完成IND申请，并通过临床试验、FDA批准和 培吉酮作为治疗HFpEF的处方药商业化。

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.