Pivotal Preclinical Studies of Novel Infusible ECM for Treating Acute MI

总结 心肌梗死（MI）后心力衰竭仍然是美国的主要死亡原因。 据估计，约55万美国人将有一个新的MI，约20万将有一个复发性MI，导致一个大的 心脏衰竭患者的身体。这些令人震惊的统计数字需要开发新的 缺血性心肌病患者的治疗方法。组织工程与再生医学策略 为开发治疗这些患者的新疗法提供了巨大的潜力。虽然细胞疗法 已被广泛研究用于治疗MI和心力衰竭，初始细胞治疗试验的荟萃分析 表明对心脏功能只有适度影响。最近脱细胞生物材料显示出巨大的前景 提供类似或更大的功能益处，而没有与细胞递送相关的并发症。可注射 刺激内源性修复的生物材料是一种有吸引力的替代物，因为潜在的治疗方法仍然可以被 通过导管以最小侵入性输送，但可以从货架上取下，并显著降低成本 与细胞产品相比。因此，Ventrix专注于无细胞再生医学方法。文特里克斯 在开发治疗缺血性心肌病的可注射生物材料方面拥有成功的历史。两 先前的NIH SBIRs导致VentriGel（一种可注射、导管输送的水凝胶）的IND获批 来源于脱细胞猪心肌。这导致了最近在患者中成功的1期临床试验 MI后60天至3年。我们最近开发了一种新的可输注ECM，用于治疗急性MI。我们证明了这 可以通过冠状动脉内输注递送至急性MI，并且其改善大鼠急性MI中的心脏功能 模拟冠状动脉内分娩后的模型。在我们以前的研究中，我们优化了 可输注ECM并在猪急性MI模型中证明了初步可行性和有效性。研究 在这个第二阶段项目中提出的是开始研究患者可输注ECM的最后步骤的一部分， 将生物材料产品推向市场的关键步骤，这将是对现有护理标准的补充。 这将是第一个用于治疗急性心肌梗死患者的冠状动脉内可输注再生生物材料产品。

Summary Heart failure post-myocardial infarction (MI) continues to be the leading cause of death in the U.S. Each year it is estimated that ~550K Americans will have a new MI, and ~200K will have a recurrent MI, leading to a large body of patients suffering from heart failure. These staggering statistics necessitate the development of new therapies for patients with ischemic cardiomyopathy. Tissue engineering and regenerative medicine strategies offer significant potential for the development of novel therapies to treat these patients. While cell therapies have been extensively studied for the treatment of MI and heart failure, meta-analyses of initial cell therapy trials suggest only a modest effect on cardiac function. More recently acellular biomaterials have shown great promise in providing similar or greater functional benefit without the complications associated with cell delivery. Injectable biomaterials that stimulate endogenous repair are an attractive alternative since potential therapies could still be delivered minimally invasively via catheter yet could be off the shelf and have significantly reduced costs compared to cell products. Ventrix is therefore focusing on cell-free regenerative medicine approaches. Ventrix has a history of success in developing injectable biomaterials for treating ischemic cardiomyopathy. Two previous NIH SBIRs resulted in an approved IND for VentriGel, an injectable, catheter-deliverable hydrogel derived from decellularized porcine myocardium. This led to a recent successful Phase 1 clinical trial in patients 60 days to 3 years post-MI. We recently developed a new Infusible ECM, for treating acute MI. We showed it can be delivered to an acute MI via intracoronary infusion and that it improves cardiac function in a rat acute MI model following simulated intracoronary delivery. In our previous studies, we optimized delivery and retention of Infusible ECM and demonstrated preliminary feasibility and efficacy in a porcine acute MI model. The studies proposed in this Phase II project are part of the final steps to initiate studying Infusible ECM in patients, and a key step in bringing a biomaterial product to market, which will be complementary to existing standard of care. This will be the first intracoronary infusible regenerative biomaterial product for treating acute MI patients.