Pivotal Preclinical Studies of Novel Infusible ECM for Treating Acute MI

摘要 在美国，心肌梗死后心力衰竭(MI)仍然是主要的死亡原因。每年 据估计，~55万美国人将有新的MI，~200K将有反复的MI，导致大量 患有心力衰竭的病人的身体。这些令人震惊的统计数字要求开发新的 缺血性心肌病患者的治疗。组织工程与再生医学战略 为开发治疗这些患者的新疗法提供了巨大的潜力。而细胞疗法有 已被广泛研究用于治疗心肌梗死和心力衰竭，最初细胞治疗试验的荟萃分析 提示对心脏功能只有轻微的影响。最近，脱细胞生物材料显示出巨大的前景 在提供类似或更大的功能益处方面，没有与细胞输送相关的并发症。可注射的 刺激内源性修复的生物材料是一个有吸引力的替代选择，因为潜在的治疗方法仍然可能是 通过导管以最小的侵入性提供，但可以下架，大大降低了成本 与细胞产品相比。因此，Ventrix正专注于无细胞再生医学方法。Ventrix 在开发治疗缺血性心肌病的可注射生物材料方面取得了成功的历史。二 之前的NIH SBIRS导致了VentriGel的IND批准，VentriGel是一种可注射的、可经导管释放的水凝胶 从脱细胞的猪心肌中提取。这导致了最近在患者身上成功的一期临床试验 心肌梗死后60天至3年。我们最近开发了一种新的不融性ECM，用于治疗急性心肌梗死。我们展示了它 可以通过冠状动脉内输注传递给急性心肌梗死，并改善急性心肌梗死大鼠的心功能 模拟冠状动脉内分娩后的模型。在我们之前的研究中，我们优化了交付和保留 并在猪急性心肌梗死模型上初步验证了其可行性和有效性。这些研究 在这个第二阶段项目中提出的是启动在患者中研究不可融合的ECM的最后步骤的一部分，以及 将生物材料产品推向市场的关键一步，这将是现有护理标准的补充。 这将是首个用于治疗急性心肌梗死患者的冠状动脉内不可融合再生生物材料产品。

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.